CHRONIC PAIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
ii
ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Chronic Pain: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83820-8 1. Chronic Pain-Popular works. I. Title.
iii
Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
[email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.
iv
Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on chronic pain. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
v
About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
vi
About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
vii
Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON CHRONIC PAIN ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Chronic Pain ................................................................................. 5 E-Journals: PubMed Central ....................................................................................................... 69 The National Library of Medicine: PubMed ................................................................................ 70 CHAPTER 2. NUTRITION AND CHRONIC PAIN ............................................................................. 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Chronic Pain.............................................................................. 113 Federal Resources on Nutrition ................................................................................................. 115 Additional Web Resources ......................................................................................................... 116 CHAPTER 3. ALTERNATIVE MEDICINE AND CHRONIC PAIN ....................................................... 117 Overview.................................................................................................................................... 117 The Combined Health Information Database............................................................................. 117 National Center for Complementary and Alternative Medicine................................................ 118 Additional Web Resources ......................................................................................................... 126 General References ..................................................................................................................... 131 CHAPTER 4. DISSERTATIONS ON CHRONIC PAIN ......................................................................... 133 Overview.................................................................................................................................... 133 Dissertations on Chronic Pain................................................................................................... 133 Keeping Current ........................................................................................................................ 139 CHAPTER 5. CLINICAL TRIALS AND CHRONIC PAIN .................................................................... 141 Overview.................................................................................................................................... 141 Recent Trials on Chronic Pain................................................................................................... 141 Keeping Current on Clinical Trials ........................................................................................... 143 CHAPTER 6. PATENTS ON CHRONIC PAIN .................................................................................... 145 Overview.................................................................................................................................... 145 Patents on Chronic Pain ............................................................................................................ 145 Patent Applications on Chronic Pain ........................................................................................ 169 Keeping Current ........................................................................................................................ 199 CHAPTER 7. BOOKS ON CHRONIC PAIN........................................................................................ 201 Overview.................................................................................................................................... 201 Book Summaries: Federal Agencies............................................................................................ 201 Book Summaries: Online Booksellers......................................................................................... 203 The National Library of Medicine Book Index ........................................................................... 210 Chapters on Chronic Pain.......................................................................................................... 212 CHAPTER 8. MULTIMEDIA ON CHRONIC PAIN ............................................................................. 213 Overview.................................................................................................................................... 213 Video Recordings ....................................................................................................................... 213 Bibliography: Multimedia on Chronic Pain............................................................................... 214 CHAPTER 9. PERIODICALS AND NEWS ON CHRONIC PAIN .......................................................... 217 Overview.................................................................................................................................... 217 News Services and Press Releases.............................................................................................. 217 Newsletter Articles .................................................................................................................... 220 Academic Periodicals covering Chronic Pain ............................................................................ 221 CHAPTER 10. RESEARCHING MEDICATIONS ................................................................................. 223 Overview.................................................................................................................................... 223 U.S. Pharmacopeia..................................................................................................................... 223 Commercial Databases ............................................................................................................... 224 Researching Orphan Drugs ....................................................................................................... 224
viii Contents
APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 229 Overview.................................................................................................................................... 229 NIH Guidelines.......................................................................................................................... 229 NIH Databases........................................................................................................................... 231 Other Commercial Databases..................................................................................................... 233 APPENDIX B. PATIENT RESOURCES ............................................................................................... 235 Overview.................................................................................................................................... 235 Patient Guideline Sources.......................................................................................................... 235 Associations and Chronic Pain .................................................................................................. 240 Finding Associations.................................................................................................................. 241 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 243 Overview.................................................................................................................................... 243 Preparation................................................................................................................................. 243 Finding a Local Medical Library................................................................................................ 243 Medical Libraries in the U.S. and Canada ................................................................................. 243 ONLINE GLOSSARIES................................................................................................................ 249 Online Dictionary Directories ................................................................................................... 250 CHRONIC PAIN DICTIONARY................................................................................................ 251 INDEX .............................................................................................................................................. 339
1
FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with chronic pain is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about chronic pain, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to chronic pain, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on chronic pain. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to chronic pain, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on chronic pain. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
3
CHAPTER 1. STUDIES ON CHRONIC PAIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on chronic pain.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and chronic pain, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “chronic pain” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Clinical Associations Between Tinnitus and Chronic Pain Source: Otolaryngology-Head and Neck Surgery. 2003;128:706-10. Contact: Send requests to:. Summary: In this article the authors report on a prospective nonrandomized study in which a survey and the Tinnitus Handicap Inventory (THI) were distributed to 72 patients (50 women and 22 men) attending a tertiary chronic pain clinic, to determine the prevalence and severity of tinnitus inpatients with chronic pain. The research findings suggest a high incidence of tinnitus in people suffering with chronic pain.
•
Use of Aromatherapy as a Complementary Treatment for Chronic Pain Source: Alternative Therapies in Health and Medicine. 5(5): 42-51. September 1999.
4
Chronic Pain
Summary: This article discusses the use of aromatherapy as a complementary treatment for chronic pain. First, it defines aromatherapy, reviews the effects of aroma on the body, and describes methods of using aromatherapy with and without touch. Then, it summarizes human studies on the use of aromatherapy in the treatment of pain, including aromatherapy for children, lavender for pain and coping, chamomile for pain in cancer, marigold for pain in hyperkeratotic plantar lesions, peppermint for headache and arthritic pain, and rose for pain in cancer with bone metastases. Finally, it reviews animal studies, and discusses the potential for untoward effects. It includes a list of essential oils with analgesic properties that are safe to use. The article has 4 tables and 96 references. •
Effective Ways to Manage Chronic Pain Source: Patient Care. 30(11):154-155,159-162,164-167,171-172; June 1996. Summary: This journal article addresses the various diagnostic and treatment considerations for patients with chronic pain. The authors explain that the keys to controlling pain and restoring function are understanding the multidimensional character of pain syndromes and engaging the full dimension of the doctor-patient relationship in the search for solutions. Both of these areas are examined, as well as the selection of a drug regimen, exercise, the use of a pain diary, and considerations when recruiting a caregiver team for case management. Nondrug therapies such as meditation and relaxation, hypnosis, cognitive therapy, biofeedback, and manipulation are also addressed, along with the invasive therapies of acupuncture, trigger- point injections, nerve blocks and ablation, and opioid reservoirs and pumps. The article concludes with a brief discussion on therapeutic objectives and follow-up. 1 reference.
•
Effective Management of Chronic Pain. The Analgesic Dilemma Source: Postgraduate Medicine. 100(3):281-284,287- 290,293,296; September 1996. Summary: This journal article for health professionals discusses the effective management of chronic pain by using prescription analgesics. The goals of chronic pain management are identified, and barriers to achieving them are highlighted. Prescription medications that can be used as analgesics for chronic pain are described, focusing on nonsteroidal anti-inflammatory drugs, opioids, and tramadol hydrochloride. Opioid use is discussed in terms of limiting factors, patient selection, and goals. Adjuvant medications that may be used in the management of selected chronic pain states are also highlighted, including antidepressants, antiarrhythmics, anticonvulsants, calcium channel blockers, antiadrenergics, and topical agents. 27 references, 1 figure, and 5 tables. (AA-M).
•
Chronic Pain: Primary Care Treatment of the Older Patient Source: Geriatrics. 54(1): 23-28,33-34,37. January 1999. Summary: This journal article provides health professionals with information on a practical, office based approach to managing older patients who have chronic pain. The prevalence of chronic diseases associated with pain increases with age, and pain prevalence appears to increase with the level of functional dependence. Chronic pain in older patients is associated with sleep disorders, impaired physical and social function, and increased health care utilization. Symptoms of pain, anxiety, and depression are often associated and may intensify one another. There is no biological marker for pain, so it is usually assessed by self report. Pain assessment tools include visual analog scales that measure pain intensity. Multidimensional assessments that offer pain descriptors
Studies
5
may provide important diagnostic clues to the underlying pathogenic process. Reports from caregivers should also be sought. Comprehensive pain assessment includes a medical history and a physical examination, as well as a psychosocial evaluation for anxiety and depression and for cognitive status and available support systems. Because a complete resolution of chronic pain is unlikely, it is important to establish early in therapy the level of pain that the patient would find acceptable. The goal of therapy is to treat chronic pain while minimizing side effects and optimizing the functional status of the patient. Pain can be managed pharmacologically with nonsteroidal antiinflammatory drugs, cyclooxygenase inhibitors, and opioids. Nonpharmacologic treatments include patient education, cognitive behavioral therapies, physical therapy, and exercise. The article uses a sample patient to illustrate important principles of diagnosing pain and prescribing pharmacologic and nonpharmacologic therapies. 4 tables and 26 references. (AA-M).
Federally Funded Research on Chronic Pain The U.S. Government supports a variety of research studies relating to chronic pain. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to chronic pain. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore chronic pain. The following is typical of the type of information found when searching the CRISP database for chronic pain: •
Project Title: A NOVEL RF TENS DEVICE FOR ACUTE PAIN MANAGEMENT Principal Investigator & Institution: Andrasik, Frank; Cyclotec Advanced Medical Technologies 4871 Nw 65Th Ave Lauderhill, Fl 33319 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Cyclotec AMT, Inc. is developing 'non-invasive' transcutaneous electrical stimulators (TENS) that may prove to be viable adjuncts to or alternatives for drugs for management of recent onset "acute" pain. TENS has long been used for "chronic" pain management. The device complexities have made them prohibitive for short-term 'acute' applications; an application for which the technology promises to be well suited for. Cyclotec's 'novel' developments for acute indications include: miniaturization, wireless operation, remote control activation, multiple pulsing features, durability, simplification of operation, extended battery life, and the capability of placement virtually anywhere on the body. The remote control (RF) features allow the stimulation devices now in development to be easily controlled by the patient - without
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
6
Chronic Pain
the extension wires necessary on all other TENS units - no matter where the units are placed on the body, e.g., back, neck, shoulder, hip, and etc. Upon completion of development of 12 functional prototype units, initial pilot investigations at various clinical sites will be performed to establish efficacy in conjunction with medication and with the absence of medication in a double-blinded study to determine effectiveness in treatment of acute pain. Should TENS prove as effective, simple and comfortable to wear by patients as the company hopes they will be, Cyclotec AMT devices will find a significant market niche as TENS has few cautions or warnings while drugs are well known to have long-term moderate to severe side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACTIONS OF PROINFLAMMATORY CYTOKINES ON SENSORY NEURONS Principal Investigator & Institution: Nicol, Grant D.; Professor; Pharmacology and Toxicology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 10-JUN-1999; Project End 31-MAR-2003 Summary: (applicant's abstract): Increasing evidence suggests that activation of various components of the immune system contribute to chronic pain and inflammation. A number of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and interleukin-6 (IL-6) are synthesized and released at sites of trauma and produce hyperalgesia in animal models of pain. One mechanism for cytokine-induced augmentation of pain perception could involve their direct actions on nociceptive sensory neurons to enhance excitability and/or sensitize them to physical or chemical stimuli. Despite abundant evidence that TNF-alpha, IL-1beta, and IL-6 produce hyperalgesia and inflammation, there is little information regarding their capacity to modulate intracellular signaling pathways that regulate sensory neuron function. The hypothesis of this proposal is that pro-inflammatory cytokines act directly on sensory neurons to enhance their excitability and sensitize these cells to noxious mechanical and chemical stimuli and, in turn, augment the release of neuroactive substances from these neurons. The proposed studies will utilize two approaches: patch-clamp electrophysiology to assess cytokine-induced alterations in membrane excitability in rat sensory neurons grown in culture and biochemical measurements of neuropeptide release in isolated sensory neurons grown in culture and an in vitro preparation of rat spinal cord slices. The aims of this proposal are: 1) to determine whether acute or chronic exposure to TNF-alpha, IL-1beta, or 1L-6 alters membrane excitability and/or sensitizes isolated sensory neurons to electrical or chemical stimuli, 2) to determine whether these pro-inflammatory cytokines stimulate and/or sensitize the release of SP and CGRP from rat sensory neurons grown in culture or from rat spinal cord slices; and 3) to determine the effects of pro-inflammatory cytokines on sphingolipid second messengers and diacylglycerol in sensory neurons and to establish causal relationships between changes in second messenger systems and cytokine-induced alterations in excitability and peptide release. Overall, the knowledge gained from these studies is critical for understanding the etiology of chronic pain and could eventually aid in designing interventions to alleviate the pain. The results of this work can increase the understanding of the cellular mechanisms mediating the interaction between the nervous system and the immune system and thus be applicable to other areas of neurobiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
7
Project Title: ACUPUNCTURE TREATMENT OF PAIN IN PANCREATIC CANCER Principal Investigator & Institution: Cassileth, Barrie R.; Chief; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): BACKGROUND: Pancreatic cancer affects approximately 28,000 Americans a year. Approximately 85-90 percent of these patients are first diagnosed when their disease already is locally advanced or metastatic. AT this point, median survival is three to six months. Treatment of pancreatic cancer is predominantly palliative in nature. Pain control is often the most serious challenge: the pancreas has an extensive blood, lymphatic and nerve supply and is surrounded by numerous other abdominal organs. More than 90 percent of patients with advanced pancreatic cancer experience moderate to severe pain. Several surgical and nonoperative procedures are used to palliate pancreatic pain, including blocking afferent pain fibers from the pancreas. Data on the efficacy of these approaches are limited and these interventions tend to be used only in select cases. Oncologic management with gemcitabine chemotherapy or radiotherapy reduces pain in a minority of patients. Most patients require opiates for pain control, and the high doses needed often cause undesirable sedation. Basic and clinical research supports acupuncture for the treatment of pain. A randomized trial found that acupuncture helps relieve non-malignant pancreatic pain, suggesting that an early phase trial of acupuncture for pancreatic cancer pain would be warranted. Objectives: To assess the effects of an acupuncture/acupressure intervention on pain, sedation and opiate medication in patients with pancreatic cancer experiencing moderate to severe pain to: i) determine whether controlled trials are warranted and ii) provide data to aid design of further warranted studies. Methods: Initially, a small number of pancreatic cancer patients reporting either high levels of pain or high levels of sedation will be treated in order to finalize the acupuncture prescription and the data collection procedures. We will then accrue patients in a standard two-stage, Phase II design. Patients will receive four sessions of a standardized acupuncture treatment with intervening acupressure over 10 days. Pain, opiate medication and sedation will be assessed for three days at baseline and post-treatment. Patients will be considered to have responded to treatment if they report a pre-specified level of improvement in either pain or sedation. Ten patients will be recruited. If less than two experience responses, the trial will be terminated. Otherwise, an additional 19 patients will be accrued. A Phase III trial will be deemed warranted if there are 6 or more responses in total; this is consistent with a 30 percent response rate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: AFFERENT PLASTICITY UNDERLYING URETHRAL AND PELVIC PA Principal Investigator & Institution: Yoshimura, Naoki; Associate Professor; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Patients with painful bladder syndromes such as interstitial cystitis (IC) characterized by urinary frequency, urgency, and bladder pain often exhibit urethral or pelvic pain. It is also documented that peripheral nerve injury in the pelvis may contribute to the emergence of bladder and/or pelvic pain because surgical manipulation of visceral organs is known to be a risk factor for the IC, and also often
8
Chronic Pain
leads to aggravation of existing symptoms or onset of new symptoms in patients with pelvic pain. The urethra, urethral sphincter muscles and the pelvic floor are innervated by a subset of visceral (pelvic and hypogastric) and somatic (pudendal) afferent fibers which are a more diverse population (C, Asigma and Abeta-fibers; possibly Aalphafibers) than those innervating the urinary bladder (C and Asigma-fibers). However, little is known about their functional characteristics and changes under chronic pathological conditions including tissue inflammation or nerve injury that may result in chronic urethral or pelvic pain. Thus, in this research project, electrophysiologic, pharmacologic, molecular and neurochemical techniques will be used to examine the characteristics of urethral afferent neurons and somatic afferent neurons in the pudendal nerve. We are particularly interested in characterizing membrane properties of these afferent neurons, and also in identifying how the chemical mediators or pathology alter ion channel and receptor properties, leading to neuronal hyperexcitability. Several hypotheses will be tested: (1) Multiple subtypes of afferent neurons can be identified based on their functional and morphological properties including tetrodotoxin-resistant Na+ channels, slow-inactivating transient K+ channels, vanilloid receptors (VR1) sensitive to capsaicin, and immunoreactivity against specific cellular markers such as neurofilament or isolectin-B4, (2) Chronic inflammation of the urethra/pelvic floor or direct injury to the pudendal nerve alters the expression of ion channels or neurotransmitter mechanisms in afferent neurons, resulting in hyperexcitability of these neurons. These changes might be different from those that we have been recently identified in bladder afferent neurons, (3) Functional changes in urethral afferent neurons or pudendal afferent neurons under chronic pathological conditions can induce bladder and/or urethral hyperactivities by reorganizing viscerosomatic reflex activities. The long-term objectives of the research program are to understand the mechanisms by which irritating or nerve-injuring stimuli in pelvic organs induce phenotypic changes in their afferent pathways and thereby trigger chronic pain in the pelvis. If a specific relation is found between different pathology and alteration in ion channel or receptor properties/expression, it is possible to identify new molecular target of drug therapy for chronic bladder and/or pelvic pain associated with painful bladder syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALTERNATIVES TO OPIOIDS FOR CHRONIC PAIN -PART III Principal Investigator & Institution: Deleo, Joyce A.; Associate Professor; Anesthesiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 15-JUL-1997; Project End 31-MAY-2005 Summary: The pain that follows nerve injury is chronic and consistently refractory to available analgesics. These neuropathic pain syndromes include deafferentation pain, diabetic, cancer and ischemic neuropathies, phantom limb pain, trigeminal neuralgia, postherpetic neuralgias and nerve injury caused by surgery or trauma. Neuropathic pain is not only chronic and intractable, it is debilitating and causes extreme physical, psychological and social distress. The broad, long- term objective pf our research is to elucidate spinal neuroimmune mechanisms responsible for the generation and maintenance of neuropathic pain. This knowledge will enable development of new medications to treat neuropathic pain without the added liability of drug abuse. Research completed in the previous funding period provides substantial data to support the role of central nervous system (CNC) cytokines in persistent neuropathic pain states. We propose to extend our studies to address the unifying hypothesis that chronic pain following peripheral nerve injury is maintained by central neuroimmune/neuroinflammatory mechanisms. The central hypothesis is that
Studies
9
peripheral nerve injury causes an inappropriate CNS expression of Major Histocompatibility Complex (MHC) Class II and cellular adhesion molecules which leads to an imbalance of proinflammatory cytokines and immune mediators that manifests as persistent neuropathic pain. This hypothesis will be tested using the following Specific Aims: 1) Assess the role of spinal MHC Class II and cellular adhesion molecule expression in nerve injury and acute inflammatory animal models; 2) Determine whether activated T-cells or macrophages are recruited into the CNS in response to a peripheral nerve injury; 3) Continue to evaluate the potential for global or specific immunosuppressive therapy yo alter sensory nociceptive processing; 4) Determine the effect of the above immunosuppressive therapy on spinal proinflammatory cytokines, MHC Class II and CAM expression. Immunocytochemistry, in situ hybridiazation, ELISA, RNS protection assays, specific pharmacological agents and noncieptive behavioral assays will be used to resolve these specific aims. When completed, these studies will provide: a) Information o the kinetics of spinal MHC class II and CAM expression following peripheral nerve injury and acute intraplantar inflammation, b) Data on the recruitment of immune cells into the CNS in response to nerve injury; c) Preliminary data to support new pharmacological approaches to the treatment of clinical neuropathic pain; d) a foundation for further understanding the neuroimmune response of nerve injury and the relationship to other central nervous systems inflammatory disease states e) Data to guide future studies that evaluate the role of cytokines and neuroimmune activation in chronic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMPA RECEPTOR BLOCKING PEPTIDES FOR CHRONIC PAIN Principal Investigator & Institution: Harty, Patrick T.; Cognetix, Inc. 421 Wakara Way, Ste 201 Salt Lake City, Ut 84108 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): We propose to isolate and identify novel AMPA receptor blocking conopeptides from marine cone snail venom for chronic pain intervention. Conopeptides are bioactive peptides from marine cone snail venom, and AMPA (a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors are nonNMDA glutamate type receptors, which mediate fast signal transmission in nociceptive pathways. AMPA receptor blocking conopeptides will be isolated from the venom and sequenced for their amino acid composition. AMPA receptor blocking drugs for the treatment of chronic pain exist, but are limited in use by a high incidence of unwanted side effects, and lack of specificity for only the AMPA type glutamate receptor. AMPA receptor involvement in chronic pain transmission occurs in the dorsal root ganglia, dorsal horn and spinal cord. Novel conopeptides that are selective for blocking AMPA receptors will provide analgesia in the treatment of chronic pain. In Phase I we will: 1) establish biologically active AMPA receptor blocking venom fractions, 2) purify identified venom fractions and sequence the individual peptides that block AMPA receptors, 3) determine the specific AMPA receptor subunits acted on by the AMPA blocking peptides. In Phase II we will determine the analgesic activity of AMPA receptor blocking conopeptides in vivo rodent models of chronic pain. PROPOSED COMMERCIAL APPLICATION: The treatment and management of chronic pain afflicts approximately 34 million Americans resulting in costs of $40 billion annually. The incidence of chronic pain is predicted to increase due to a rise in the aging population. In many instances chronic pain is not well managed through current therapies, especially due to the addictive nature of narcotics used to treat chronic pain.
10
Chronic Pain
Therefore, an increasing demand for non-opioid analgesics could be met by effective conopeptide analgesics in this market. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURALGIA
ANALGESIA
IN
HERPES
ZOSTER
AND
POSTHERPETIC
Principal Investigator & Institution: Dworkin, Robert H.; Professor; Anesthesiology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Herpes zoster is a common and painful neurological disease that is caused by reactivation of the varicella-zoster virus. Herpes zoster pain that persists after healing of the acute infection is termed postherpetic neuralgia (PHN), a chronic pain syndrome that is often refractory to all treatment. The prevalence of PHN is expected to increase substantially in the coming decades because the incidence of herpes zoster and the risk of PHN will both increase as the population ages. Although research to improve treatment is continuing, as many as half of all patients do not currently obtain relief. For this reason, the development of interventions that prevent PHN would lead to major reductions in disability, distress, and use of health care resources. On the basis of the results of research on risk factors for PHN and its pathophysiologic mechanisms, it can be hypothesized that combined antiviral and analgesic treatment begun as soon as possible after the -onset of herpes zoster will reduce the risk of PHN. The specific aim of this planning grant is to develop the protocol and procedures for a clinical trial to test this hypothesis. The proposed trial will have the following major objectives: The primary aim will be to test the hypothesis that the risk of PHN is reduced by half in herpes zoster patients treated with an antiviral agent and an opioid analgesic compared with patients treated with the antiviral agent and matching placebo. Support for this hypothesis would have a major impact on the treatment of patients with herpes zoster and lead to a substantial reduction in the prevalence of PHN. A second major aim that will be accomplished by the proposed trial is determining whether the initiation of central mechanisms of chronic neuropathic pain can be prevented by attenuating acute pain. The answer to this question will provide important information about mechanisms of prolonged pain and have major implications for its prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALGESIC EFFECTS OF ADRENAL CHROMAFFIN CELL TRANSPLANTS Principal Investigator & Institution: Pappas, George D.; Professor; Anatomy and Cell Biology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Transplantation of same species (allogeneic) chromaffin cells from the adrenal gland to the central nervous system has been widely shown to produce profound analgesia. This was first demonstrated in rats, but the technique has also successfully alleviated pain in more than 35 cancer patients. After spinal transplant, these patients show a distinct increase in spinal fluid levels of endogenous opioids and catecholamines, with a robust analgesic effect. The effects last many months and are accompanied by a definite inhibition in the development of tolerance to exogenous opiate analgesic drugs, a common problem with these patients. Thus transplantation of allogeneic chromaffin cell graft clearly shows potential as a
Studies
11
means of treating chronic, intractable pain. Unfortunately, transplantation of allogeneic chromaffin cells has limitations similar to other transplants, e.g., the availability of suitable human tissue. To meet this challenge, xenogeneic (cross-species) transplants have demonstrated clear analgesic effects in rodents. However, there are significant roadblocks in transferring this method to humans. Earlier work indicates that purification of bovine or porcine cells minimizes rejection potential in rats. Preliminary work also indicates that embedding cells in a collagen matrix may improve their viability and analgesic potential. However, prior to attempting cross-species transplants in humans, it is critical to examine these effects in detail in species that are much closer to man immunologically and neurophysiologically, namely nonhuman primates. Thus, the work proposed here entails investigations designed to optimize the analgesic potential of xenogeneic chromaffin cells when transplanted into primates. The experiments will determine, in vitro, the effects of seeding cells in collagen matrices on the viability, integrity, and rejection potential of purified chromaffin cells. In vivo experiments will take these preparations to monkeys, investigating cell-dose dependence and collagen matrix effects on the analgesic efficacy of xenogeneic transplants. In this way, we hope to move much closer to the capability of treating patients with severe chronic pain with a novel treatment that is long-lasting and not only does not precipitate tolerance, but also appears to impede its development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALGESICS FOR CHRONIC PAIN TREATMENT IN THE ELDERLY Principal Investigator & Institution: Narducy, Kenneth W.; St Charles Pharmaceuticals 478 Broadway St New Orleans, La 70118 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-DEC-2001 Summary: adapted from applicant's abstract): Acetaminophen, a nonsteroidal antiinflammatory drug (NSAID), is widely used for treatment of pain and/or fever in the elderly. This dual action is sometimes contraindicated. In many instances pain needs to be controlled without masking the symptomatic fever (e.g., postoperative period). Acetaminophen can also cause hepatotoxicity, particularly after ingestion of large doses or chronic use of smaller doses (especially in the elderly or when liver function is affected) that can lead to death. Therefore, there is a need for new more selective compounds with greater pharmacological potency and devoid of hepatotoxic or antipyretic effect. We are exploring a series of new proprietary derivatives of acetaminophen. In preliminary studies, one of these compounds (SCP-1) demonstrated high analgesic activity free from antipyretic activity and hepatotoxicity. In this STTR project we propose to further characterize SCP-1 and compare biological properties with acetaminophen. We will also explore combinations of SCP-1 with morphine (and with other pain relievers) to confirm preliminary studies indicating a synergistic effect of this combination. The Phase I experiments will help us ascertain the legitimacy of SCP-1 as a lead candidate drug worthy of further development and testing in Phase II for the treatment of chronic and post-operative pain in the elderly. PROPOSED COMMERCIAL APPLICATION: The market for pain relievers in the US is estimated to be $4 billion annually. Acetaminophen (marketed under the name Tylenol(TM) and other brand names) represents about 40% of that market. Although widely used, acetaminophen is not without some serious side effects. There is a clear unmet medical need for pain relievers that are effective but have a better safety profile than acetaminophen. The research proposed in this grant application is directed at developing a pain reliever that is as effective as acetaminophen but with fewer side effects. This drug would be targeted at those patients most at risk from acetaminophen toxicity, the elderly, particularly those
12
Chronic Pain
who must take pain relievers on a chronic basis, and those experiencing post-operative pin where masking the symptomatic fever could delay the diagnosis of infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRIEF FOCUSED TREATMENT FOR TMD: MECHANISMS OF ACTION Principal Investigator & Institution: Litt, Mark D.; Behav Scis & Community Health; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: (provided by applicant): TMD is a widespread chronic pain condition. Successful psychosocial treatments for TMD have been developed, but the mechanisms by which these treatments achieve their effects are not well known. The goal of this project is to evaluate the possible mechanisms responsible for treatment gains in TMD treatment. Men and women (N=106) with complaints of chronic facial pain for at least 3 months' duration will be recruited from the University Dental Clinics and from the community via advertisements and randomly assigned to either a Standard Conservative Treatment (STD) employing an intraoral splint plus anti-inflammatory agents, or to a Standard Treatment + Cognitive-Behavioral Treatment Program (STD+CBT), that will include standard treatment but also focus on changing self-efficacy and decreasing catastrophization. Both treatments will entail 6 clinic visits. Dispositional and situational variables derived from a comprehensive model of pain coping will be measured before and after treatment. The situational variables, including coping responses, mood states, situational appraisals and self-efficacy, will be measured in an experience sampling paradigm four times daily using a hand-held computer. This will be done to minimize retrospective biases that may have hampered earlier studies of treatment process. Dependent variables will be self-report measures of distress, pain, and interference with activities, as well as blood plasma levels of cortisol and selected cytokines, measured at the end of the 6-week treatment period, and at follow-up points thereafter up to a 12-month follow-up. It is expected that the STD+CBT treatment will result in measurable changes in constructs such as self-efficacy and catastrophization, and that these changes will be related to improved outcomes compared to the STD controls. It is also expected that outcome differences between groups will be associated with changes in inflammatory mediators (cytokine levels). Finally, it is suggested that changes in situational treatment process variables will be associated with changes in cytokine levels. The results may indicate the true active mechanisms of successful TMD treatment, if these mechanisms can be successfully identified it would have important implications for the development of more effective treatment programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CAPSAICIN RECEPTOR SUBTYPES IN PAIN TRANSDUCTION Principal Investigator & Institution: Schumacher, Mark A.; Anesthesia and Perioperative Care; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2006 Summary: (provided by applicant) Despite intense efforts to effectively treat acute and chronic pain, current therapies are still associated with significant side effects including central nervous system depression, development of tolerance and risk of addiction. Since the majority of acute and chronic pain is maintained by the persistent activation of specialized sensory neurons, the selective blockade of pain sensing nerve terminals could represent a novel way to treat pain with fewer unwanted side effects. Recent
Studies
13
advances have been made in the characterization of receptors and ion channels that function to detect painful noxious stimuli. Notably, the vanilloid (capsaicin) receptorVR1 has been isolated and is undergoing intense characterization to determine whether it can direct sensory nerve activation in response to painful stimuli. Because the response properties of sensory neurons are complex, we have investigated whether other related receptor / ion channels exist in sensory neurons. This effort has revealed the existence of vanilloid receptor splice variants. VR.5'sv is one such variant that we isolated that appears insensitive to capsaicin and other noxious stimuli. In this proposal, we are testing the hypothesis that VR.5'sv can block the activation of VR1 in response to noxious stimuli when both proteins are expressed together. Another vanilloid receptor splice variant originally identified in kidney by another laboratory was found to have mechano-sensitive properties and therefore is termed "stretch inactivated channel." SIC is activated by cell shrinkage, and based on its pattern of expression in sensory neurons, it may participate in the detection of noxious hypertonic conditions. Comparison of SIC to VR1 and VR.5'sv has revealed a unique structural feature that could help explain its ability to couple changes in cell shape into channel activation. We propose to study this feature in the hope to better understand how noxious mechanical stimuli are detected by sensory neurons. Although our understanding about VR1 and its splice variants have grown, little is known about what factors control their abundance in the sensory nerve terminals. Using genomic fragments isolated upstream from the vanilloid receptor gene and inserted into reporter plasmids, we will test the hypothesis that tissue derived growth factors positively regulate the amount of RNA encoding VR1 in sensory neurons through their effect on RNA transcription. Moreover, using this assay system, we hope to determine in general what factors regulate VR1, VR.5' sv and SIC. Determining bow these factors increase or decrease the transcription of VR subtypes will provide a potential means to modulate pain transduction and hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CGX-1160, A NON-OPIOID, BROAD-SPECTRUM ANALGESIC Principal Investigator & Institution: Wagstaff, John D.; Cognetix, Inc. 421 Wakara Way, Ste 201 Salt Lake City, Ut 84108 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-JUL-2002 Summary: (provided by applicant): The goal of this proposal is to establish the efficacy of contulakin-G (CGX-1160), a newly discovered analgesic conopeptide for the treatment of chronic pain. Currently chronic pain is treated with a variety of analgesic and adjuvant drugs including: opioids, tricyclic antidepressants, anticonvulsants, and local anesthetics. A significant number of patients, particularly those suffering from neuropathic pain, are refractory to all of the currently available drugs. Furthermore, all of these compounds have significant, dose- and treatment-limiting side effects. Preliminary data suggest that CGX-1160 is an extremely potent analgesic in animal models of persistent pain following intrathecal administration, with a wide separation between efficacy and toxicity, and may represent an alternative therapy for intractable pain. In phase I we will demonstrate the efficacy of CGX-1160 in a broad range of animal pain models including: acute, persistent inflammatory, chronic inflammatory, and neuropathic pain. A series of closely related analogs will be synthesized and compared to the native conopeptide for their in vivo efficacy, and resistance to endogenous peptidases. We will attempt to determine the specific mechanism of action through in vivo and in vitro pharmacological methods. We will also compare the toxicity profile of this compound with morphine. These studies will determine a behavioral therapeutic index for the compounds tested. This will determine which of the analogs will be further
14
Chronic Pain
characterized in formal toxicology testing. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHIMERIC PEPTIDES AS NOVEL ANALGESICS Principal Investigator & Institution: Kream, Richard M.; Professor of Pharmacology; Biochemistry; Suny Downstate Medical Center 450 Clarkson Ave New York, Ny 11203 Timing: Fiscal Year 2001; Project Start 15-JAN-2001; Project End 31-DEC-2004 Summary: (Adapted from applicant's abstract) Important medically-related issues exist as to why acute pain is perceived with high intensity despite the presence of extensive endogenous pain-modulating systems, and why chronic intractable pain arises from pathophysiological sequelae of nerve injury without consistency of symptomatology, etiological factors; and treatment strategies across patient populations. This necessitates an in depth understanding of how spinal excitatory systems, of which the tachykinin substance P (SP) represents a prototypic regulatory peptide, functionally interact with endogenous opioid systems to maintain functional homeostasis of nociceptive signaling and compensatory antinociceptive responsiveness at spinal and supra spinal levels. The foundation of present proposal is based on recent data obtained from in vivo pharmacological testing, and complementary biochemical analyses, of a chimeric peptide newly synthesized by our group: a heptapeptide consisting of overlapping NH2- and COOH-terminal functional domains of the opioid endomorphin-2(EM-2) and SP, respectively. The chimeric molecule YPFFGLM-NH2, designated ESP7, displays agonist activity at both the u-opioid (MOR) and SP (SPR) receptors. Administration of low concentrations of ESP7 by the intrathecal route produces long-lasting analgesia in the rat tail-flick text that is blocked by prior treatment with the opioid antagonist naltrexone. Repeated administration of ESP7 produces opioid-dependent analgesia without loss of potency over five days. In contrast, repeated administration of ESP7 in the presence of the selective SPR antagonist RP67580 results in a rapid loss of analgesic potency consistent with the development of opioid tolerance observed following administration of MOR-preferring opioids; post-hoc administration of ESP7 also effects partial rescue of opioid responsiveness in tolerant animals. We conclude that in vivo activation of SPR-expressing spinal neurons is functionally linked to inhibition of or delayed onset of opioid tolerance, and further hypothesize that coincident activation of MOR- and SPR-expressing systems mimics an ongoing state of reciprocal excitation and inhibition normally encountered in nociceptive processing. Our overall testable hypothesis is thus: chimeric peptides, composed oftwo independent but overlapping moieties contributed by an opioid peptide and substance P, are novel non-tolerance forming analgesics via their combined agonist action at functionally interactive classes of spinal and supra spinal receptors.Within this framework we propose the following three Specific Aims. 1. To evaluate chimeric peptides as novel analgesic agents through targeting of interactive spinal and supra spinal opioid and tachykinin neural systems, 2. To evaluate chimeric peptides in preclinical models of opioid tolerance and of acute and chronic pain, 3. To develop chimeric peptides with overlapping but distinct functional moieties derived from NH2-terminal domains of delta and kappa opioids and the COOH-terminal domain of SP as novel analgesics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CHRONIC LOW BACK PAIN AS A MODEL OF FIBROMYALGIA Principal Investigator & Institution: Clauw, Daniel J.; Associate Professor; Medicine; Georgetown University Washington, Dc 20057
Studies
15
Timing: Fiscal Year 2001; Project Start 15-JUN-1999; Project End 31-MAY-2003 Summary: Fibromyalgia (FM) is defined by a history of widespread pain, and the finding of tender points on examination. Arguably the two most discriminating features of FM are: 1) a generalized disturbance in pain perception, and 2) elevated levels of pronociceptive neuropeptides in the cerebrospinal fluid. The first feature, pain induced by a normally non-painful stimuli, is not surprising since this is a defining feature of FM. But it is not certain how tenderness relates to pain, since population based studies have demonstrated that not all persons who are tender have pain, and vice versa. And it has recently become clear that tender points are a poor measure of a person's inherent tenderness. The meaning of these elevated levels of CSF neuropeptides is likewise unclear. These findings may not be specific for FM, and may be the cause of pain and/or tenderness, or may be the result of pain, tenderness, or some other process. Chronic lower back pain (CLBP) is among the most common medical problems in industrial societies. Despite this, little is actually known about the precise cause for most cases of CLBP. Anatomic and psychosocial factors have been demonstrated to predict only a small portion of the variance in the degree of pain or disability in CLBP. In preliminary studies in CLBP, we have demonstrated that tenderness predicts a significant percentage of the variance in both functional status and pain, more than either the severity of path-anatomical abnormality (i.e., X-ray/MRI),or by psychosocial factors. In a small pilot study of a subset of these patients tenderness was correlated with CSF levels of pro-nociceptive neuropeptides. There are 3 specific aims in the proposed study: 1) To confirm in a cross-sectional study of 200 CLBP patients that pain sensitivity predicts more variance in clinical outcome (e.g. functional status, pain level, Roland index) than either anatomic or psychological factors. Furthermore, we will demonstrate that pain sensitivity is an independent trait, and not a surrogate for psychological factors such as depression, anxiety, or work-related stressors. 2) To demonstrate that an individual's global pain sensitivity is determined primarily by physiologic factors (e.g. neurotransmitters in cerebrospinal fluid) and modified by psychosocial factors (e.g. cognitive and behavior influences on pain perception). We will measure the CSF concentrations of pro-nociceptive peptides such as Substance P and Nerve Growth Factor, and hypothesize that the levels of these substances largely determine an individual's global pain sensitivity. This testing will be done in patients with CLBP and FM, as well as sedentary and non-healthcare-seeking controls. 3) To use alternative methods of pain assessment that are much less influenced by psychological factors (e.g., scaling methods, Multiple Random Staircase), using both pressure and thermal stimuli, to examine the true meaning of tender points, and the relationship between these results, and the results of the above noted physiologic and psychologic parameters in individuals with FM and CLBP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC OPIOID SELF ADMINISTRATION IN THE PRESENCE OF NEUROPATHIC PAIN Principal Investigator & Institution: Martin, Thomas J.; Associate Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Extensive study of opioids has generated much information regarding the mechanisms of their analgesic and reinforcing properties. Distinct anatomical pathways have been elucidated for the antinociceptive and reinforcing properties of opioids using antagonists and neurotoxin- induced lesions of specific neuronal populations. However, these two important aspects of opioid pharmacology have largely been studied in
16
Chronic Pain
isolation. The analgesic effects of opioids are studied in the laboratory following passive administration, in which the animal does not control the dose or dosing interval. Similarly, the reinforcing effects of opiates are studied in the laboratory in the absence of pain, and little is known regarding the relevance of reinforcing mechanisms identified in this manner to the clinical use of opioids for pain relief. This project seeks to examine the pharmacology of opioids using a self-medication paradigm in rats with nerve injury. These studies will focus on the development of opioid tolerance in the presence of pain and exploration of the mechanisms of tolerance. Dosing will be accomplished through self-administration, in which the animal is allowed to determine the drug quantity necessary to achieve the desirable pharmacological effect. This technique has proven to be invaluable in the study of drug abuse, but is being applied in this project to the study of pain mechanisms and should provide equally invaluable information. Experiments are designed to determine receptor mechanisms related to the development of tolerance as well as to develop strategies for minimizing the development of tolerance and selfdetermined dose escalation through experiments using 24 hr self-administration. Preliminary data show that animals rapidly escalate opioid intake when given 24 hr access to self-administration, and that tolerance to the anti-allodynic effects of opioids results. Initial strategies include using drugs of differing efficacies and a dose-fading procedure to determine the optimum maintenance dose that minimized total dose escalation over time. Intrathecal agents will then be given as adjuvant analgesics as another strategy to inhibit or retard the development of tolerance to opioids and subsequent dose escalation. Parallel clinical studies are proposed to address these concerns in patients self-administering opioids. These studies will hopefully identify mechanisms of tolerance to opioids self- administered for pain relief and strategies to minimize such effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC PAIN IN THE 65+: EVALUATING FUNCTIONAL IMPACTS Principal Investigator & Institution: Rudy, Thomas E.; Professor and Director; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-AUG-2006 Summary: Chronic pain plagues approximately 50 percent of community dwelling older adults, and may cause significant disruption of physical, psychosocial, and cognitive function. Despite the prevalence of this potentially devastating problem, well-controlled studies of chronic pain in older adults that use a comprehensive multidimensional model are lacking. Chronic low back pain (CLBP) is among the most common chronic pain conditions of older adults, affecting approximately 6 million individuals in the United States who are greater than or equal to age 65. CLBP offers a robust model with which to study the comprehensive functional effects of chronic pain in the older adult because of the reliable and valid measures of observed physical capacity, self-reported disability and pathology that have been developed specifically for patients with low back pain. The purpose of this investigation is to broaden our understanding of disability in the older adult with chronic pain. Specifically, we will explore (1) the magnitude of the effect of CLBP on physical, psychosocial, and cognitive functioning in 200 community dwelling older adults greater than or equal to age 65 as compared with 200 pain-free control subjects, (2) the impact of CLBP associated psychosocial and neuropsychological dysfunction on physical function, and (3) whether older adults with chronic pain can be classified using a multiaxial taxonomy that has been demonstrated
Studies
17
in younger chronic pain patients. The laboratory-based physical capacities testing protocol is designed to assess body mechanics, endurance and coordination using ergonomically relevant tasks (e.g., lifting, reaching). Other comprehensive multidimensional assessment measures will include those that have particular relevance to older adults, such as pain intensity, clinical measures of physical performance, disability, sleep, mood, self- efficacy, detailed measures of neuropsychological function, and self perceptions of health and well-being. This study represents the first wellcontrolled, comprehensive examination of the effects of chronic pain on individuals who may be most threatened by the risk of functional decline, that is, community dwelling older adults. Once the effects of chronic pain have been comprehensively described, only then can effective treatment programs be developed to help ameliorate the suffering of these older Americans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC PAIN MANAGEMENT IN PRIMARY CARE Principal Investigator & Institution: Von Korff, Michael R.; Senior Investigator; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JAN-1989; Project End 31-AUG-2004 Summary: This research seeks a more effective and cost-effective integration of medical care and self-care for chronic and recurrent pain in pr5imary care settings. Aim 1: Identify improved methods for analysis of automated health care and medicine use data for TMD pain, headache and back pain patients. Identify potentially modifiable determinants of long-term frequent use of health care and pain medications for these conditions. Study One: We will study determinants of health care and prescription medicine use for pain over a five-year time span. {{Methods for analysis of automated health care and medicine use data will be assessed to test more powerful and informative approaches. Using improved analytic methods,}} we will assess the ability of patient variables to predict and explain frequent use of health care, opioid medications and sedative- hypnotic medications for patients with TMD (n=391), back pain (n=833) and headache (n=869) over a five year time-span. Aim 2: Evaluate the effectiveness of Self-Care Group interventions guided by a stepped care model. Study Two: Data from two randomized controlled trials of Self- Care Groups (SCG) initiated in 1996-98) as part of the current Program Project will be used to identify factors influencing the long-term effectiveness of SCG (participation, baseline severity, self-care orientation, prognostic variables). Study Three: A new randomized controlled trial will evaluate Self-Care Groups fully integrated into primary care. This trial will evaluate the initial benefits and the long-term effectiveness of Self-Care Groups among actively recruited back pain patients (n=250). The intervention will target patients with enduring activity limitations and higher use of health care for back pain {{Patients with continuing activity limitations will receive more intensive intervention according to a stepped care protocol.}} Patients will be followed-up 2, 6, 12 and {{24}} months after randomization. The primary outcome will be activity limitations (Roland Disability Score with added items concerning occupational role disability). Aim 3: Assess the impact of Self-Care Groups (SCG) on long-term health care and prescription medication use. Determine the effect of SCG on health care costs. Study Four: Using automated health care and medicine use data and improved analytic methods, we will investigate the long-term effects of SCG on: (1) use of health care; (2) use of prescription pain medications; and (3) health care costs for back pain (total n from three SCG trials=731). Since the SCG interventions have been shown to reduce worry, enhance confidence in self-care, and
18
Chronic Pain
reduce activity limitations, this research will provide an experimental test of whether modifying these factors reduces subsequent use of health care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC PAIN TIVR TO PREVENT PRESCRIPTION DRUG ABUSE Principal Investigator & Institution: Naylor, Magdalena R.; Psychiatry; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): This is an R21 application by a new investigator to utilize Interactive Voice Response (IVR) to develop a new strategy for preventing prescription drug abuse in patients with persistent pain. IVR is a computer-based, automated telephone that enables callers to respond to a recorded voice via the telephone keypad. Using this technology, we developed Therapeutic IVR (TIVR) as an intervention in patients using prescription medication for chronic pain. The TIVR reinforces group Coping Skills Training (CST) given in our pain clinic. It includes an automated daily diary for self monitoring, guided behavioral rehearsals of key CST coping skills, and monthly personalized feedback, all of which can be accessed by patients on demand. In our pilot test, ten subjects with severe, chronic musculoskeletal pain participated in 10 weeks of group CST followed by four months of TIVR. Subsequently, we recruited a second sample of eight patients as a comparison group who were given group CST but not the TIVR. Within subjects analysis (ANOVA) of the TIVR group showed that, compared to baseline values, the maximum mean positive change for nearly all outcome measures occurred at the post TIVR point. Several measures were significantly improved post TIVR despite lack of significance after CST. These included SF-36 Mental Health Composite Score (p<.0004), MPQ pain (p<.01), CSQ Catastrophizing (p<.0006), TOPS Total Pain Experience (p<.03) and Perceived Family/Social Disability (p<.02). Between subjects analysis (ANCOVA) of TIVR treatment and comparison groups revealed significantly higher TIVR group scores for TOPS Total Pain Experience (p<.01), TOPS Perceived Social Disability (p<.002) and SF36 Mental Composite (p<.05). Finally, Hierarchial Linear Regression of the TIVR daily diary confirmed significant reductions in the highest level of pain (p<.0001), highest stress level (p<.0001), and frequency of resorting to maladaptive coping skills such as catastrophizing (p<.0001). Analyses of these daily data also revealed a significant (.0002) decrease in the use of medication during the TIVR trial. However these latter results are tentative since we asked only two general questions about medication use, and neither question related to specific types of medication. This R21 would enable us to pretest a revised TIVR designed specifically to monitor and reduce reliance on medication and to prevent prescription drug abuse in patients with persistent pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: COGNITIVE-BEHAVIORAL THERAPY FOR VULVODYNIA Principal Investigator & Institution: Masheb, Robin M.; Associate Research; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 18-SEP-2000; Project End 31-AUG-2003 Summary: (adapted from the investigator's abstract): The proposed study aims to benefit women with vulvodynia. This newly identified women health problem may affect as many as 15 percent of women who seek gynecological care, yet little attention is given to this condition and it is frequently dismissed as psychosomatic. In 1998, the National Institute of Health called for systematic epidemiologic, etiologic, and
Studies
19
therapeutic studies of vulvodynia. The purpose of the present study is to address the need identified by the NIH, and assess the efficacy of a psychosocial treatment for vulvodynia. The primary aim of the present study is to evaluate the efficacy of a wellestablished psychosocial intervention, i.e. cognitive-behavioral therapy that has been shown to decrease pain severity, disability, and affective distress for various chronic pain conditions. The study will test the hypothesis that cognitive-behavioral therapy, relative to supportive psychotherapy, will result in substantial improvement in pain, severity, disability, and affective distress. The proposed study is a randomized twotreatment condition CBT versus supportive psychotherapy by three evaluation period (pretreatment, post-treatment, and six-month follow-up), repeated measures, and factorial design. Sixty participants with vulvodynia will be randomly assigned to either CBT or Support for 10 weeks. Empirically supported outcome measures will be used to assess pain severity, disability, and affective distress. Medication and healthcare use, global improvement, and sexual activity will also be measured. Research findings from this study, in particular with the use of empirically supported treatment outcome measures, may serve as background for the planning of larger comparative studies. Clinically, results from this study may provide a justified treatment option for women with vulvodynia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORTICAL PATHOPHYSIOLOGY OF PAIN Principal Investigator & Institution: Apkarian, Apkar Vania.; Associate Professor; Physiology; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 31-DEC-2002 Summary: (Adapted from the Investigator's Abstract) This proposal is in response to the BIOBEHAVIORAL PAIN RESEARCH RFA PA-99-021. It is a COMPETING CONTINUATION application for grant NS 35115 funded from 5-1-96 to 4-30-99. In the last funding period we developed a new functional brain imaging paradigm, using functional magnetic resonance imaging (fMRI), that enables us to parcel cortical activity associated with painful stimuli along a stimulus-suffering from chronic Reflex Sympathetic Dystrophy (RSD) pain show prefrontal hyperactivity. These abnormal activations are reversed to that seen in normal subjects after a sympathetic block. Given the new paradigm and our observations in chronic pain patients and normal volunteers we propose to extend the studies to extend the studies of the pathophysiology of chronic pain by testing specific hypotheses, designed to distinguish between two chronic pain states: Specific Aim 1 tests the hypothesis that chronic low back pain with radicular involvement can be differentiated from acute low back pain, and from normal subjects by functional brain imaging studies. These studies are designed to image brain activity directly related to the pain from which the patients suffer. The acute back pain patients are studied before and three months after spinal cord surgery. Specific Aim 2 tests the hypothesis that chronic RSD pain with allodynia is distinct from chronic RSD pain with only hyperalgesia, and that chronic RSD pain is distinguishable from chronic low back pain. The studies are done using fMRI and again are designed to directly study the pain from which the patients suffer. Specific Aim 3 tests the hypothesis that chronic pain states are associated with brain biochemistry abnormalities, and that different chronic pains may be differentiated by brain biochemistry. Hydrogen-Magnetic Resonance Spectroscopy (MRS) will be used to examine different brain regions and chemicals in RSD and low back pain patients and compared to normal subjects. Specific Aim 4 tests the hypothesis that chronic pain is correlated with cognitive abnormalities. RSD and back pain patients will be tested on a battery of cognitive tests: Stroop, WCST,
20
Chronic Pain
and Bechara's Gambling test. The chosen tests examine different frontal abilities and may differentiate between types of chronic pain. Overall the studies are designed to examine chronic pain by functional imaging, brain biochemistry, and cognitive abilities. The results, if successful, have the potential of being used in the clinic as diagnostic or prognostic tools. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DELVING INTERVENTION AND MINDBODY INTEGRATION Principal Investigator & Institution: Price, Cynthia J.; Physiological Nursing; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): In clinical practice, symptoms of dissociation and lack of bodily self-awareness are frequently associated with chronic physical pain and/or psychological distress due to illness, stress or trauma. These factors are thought to hinder the recovery processes, prompting mind-body researchers to examine alternative therapeutic approaches. The long-term goal of this research is to develop a foundation for research in body-oriented psychotherapy with bodywork as an integral component of the therapy. The immediate purpose of this proposal is to examine the effects of 'delving,' a body-oriented psychotherapy approach developed to facilitate integration of psyche and soma through bodily awareness. The specific study aims are to examine the efficacy of delving compared to massage, and to explore change associated with the therapeutic process across time. The study uses a 2-group, repeated measures design with 40 participants randomized to experimental or control group. Repeated-measures ANOVA, trend analyses, and correlational techniques will be used to test outcome efficacy and to explore the hypothesized intervention processes. This study is novel because it combines bodywork with highly specified focusing processes. Its significance lies in exploration of integration processes to enhance understanding of dissociation in general and of bodily self awareness in mind-body healing and health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: DEPRESSION AND CHRONIC PAIN IN MARRIAGE Principal Investigator & Institution: Cano, Annmarie; Psychology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The principal investigator (PI) is requesting five years of funding through the Scientist Development Award for New Minority Faculty (K01). The career development goals described in this application include testing an integrative model of depression and chronic pain developed by the applicant and training in theoretical and conceptual issues, advanced longitudinal statistical methods, objective interview assessment of life events, observational research methods with couples, and the responsible conduct of research with ethnic minorities. These activities are expected to build on the Pl's strong research and clinical background in marriage and enhance her ability to produce sophisticated scholarly work. Major depression and chronic pain are costly public health problems in the United States that are highly comorbid with each other. Although research suggests that marital variables may contribute to depression, researchers have yet to integrate existing theory and empirical findings into a comprehensive model that accounts for the interrelationships between marital functioning, chronic pain, and depression. Building on the career development activities described in the application, the PI will test an integrative model of the
Studies
21
comorbidity of chronic pain and depression in which marital functioning plays a key role. The long-term objective of the study is to develop marital treatments for individuals experiencing both depression and chronic pain. The specific aims of the study include examining how changes in general marital functioning (e.g., marital satisfaction, affect expressed in a marital interaction, marital stressors), pain-specific marital functioning (e.g., spouse responses to pain, affect expressed in a marital interaction related to the impact of pain on the couple), and pain factors (e.g., pain severity, disability) relate to changes in depression over time. Participants will be 160 married couples in the community in which one spouse has a chronic musculoskeletal pain problem. Participant couples will complete surveys, a diagnostic interview for major depression, a life events interview, and two videotaped marital interactions. Participants will also take part in 6- and 12-month follow-ups in which they will complete the same instruments. Participants will be paid upon completion of each phase of the study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF GENE THERAPY FOR CHRONIC PAIN Principal Investigator & Institution: Johns, David C.; Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Chronic pain represents a major health problem in the world today. In many cases the generator for neuropathic pain appears to be in the peripheral nervous system. Thus delivery of gene vectors to primary afferents has potential to decrease pain. Manipulation of gene expression in dorsal root ganglion cells can also be used as a tool to understand better peripheral neural mechanisms of pain. The development of an effective gene therapy requires a multifaceted approach. These can be separated into three broad headings; 1) the choice of gene to be delivered, 2) the development of an ideal delivery vector, and 3) control of the expression of the delivered gene. Adenoviral vectors with improved neurotropism are being created by manipulating the fiber gene either by altering its natural tropism through genetic manipulation, or by using fibers from different adenovirus serotypes that have different cellular tropisms. Control of gene expression will be accomplished using a modified ecdysone system that allows tighter control of expression as compared to earlier versions. To enhance neuronal selectivity, we are constructing vectors that express the ecdysone receptors from a neuron specific promoter. Transduction of target cells (as well as non-target cells) will be monitored using sensitive techniques for tracking the viral vector in vivo. The genes we propose to examine are of two types. The first gene encodes the inwardly rectifying potassium channel, Kir2.1. Expression of Kir2.1 in neurons will reverse a salient change associated with neuropathic pain, namely increased excitability. We propose to measure the level of excitability using electrophysiological (patch clamp and other methods) and behavioral techniques. The other gene of interest encodes the alpha 2 delta calcium channel sub-unit. This protein appears to be crucial for the action of gabapentin, a drug that has been widely used in treating neuropathic pain in humans. In addition, alpha 2 delta is up regulated in at least one animal model of neuropathic pain. The effects of both increasing and decreasing alpha 2 delta expression will be monitored both in vitro and in vivo by a combination of electrophysiological and behavioral techniques. In conclusion, our proposal will look to combine improved vector development with novel recording techniques to monitor closely the efficacy of gene transfer and to also assess these treatments behaviorally in animals.
22
Chronic Pain
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF OPIOIDS ON SLEEP AND FATIGUE Principal Investigator & Institution: Dimsdale, Joel E.; Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The goal of this R21 application is to refine an experimental design to examine the impact of commonly used pain medications on sleep and next-day fatigue. However, before such studies can be conducted in patients with acute or chronic pain associated with cancer or other severe chronic illness, crucial information is needed to optimize the study design. This proposal seeks to answer certain experimental methodological design questions that can be safely, quickly, and inexpensively addressed in healthy volunteers. This R21 application will generate data guiding the research design and power estimates for subsequent RO1 applications intended to address the impact of pain medication on sleep and fatigue in patients with acute or chronic pain. There are 5 specific aims: 1. Characterize the effect of a typical nighttime dose of MS-Contin and methadone on cytokines, polysomnographic sleep and on rest/activity patterns in healthy volunteers: 2. Characterize daytime fatigue the day after drug administration with self-reported measure of fatigue and mood 3. Characterize neuropsychological performance on the day after drug administration. 4. Estimate the covariance structure of sleep measures to assess the comparative advantages of a crossover or parallel groups design. 5. Evaluate the necessity of repeated first nights and whether this is the optimum design for follow-up studies. Over a two-year period, 50 healthy volunteer subjects will be examined with polysomnography, actigraphy, and neuropsychological tests. Data will be collected on self-reported mood and fatigue, as well as proinflammatory cytokine levels (IL-6, IL1beta, and TNF-alpha. The study design involves a double-blind, placebo-controlled crossover. Each individual will be admitted to the UCSD GCRC on 3 pairs of nights. Each admission will feature an acclimation night in the sleep laboratory followed by a night providing placebo, MS-Contin (15 rag) or methadone (5 mg). On the morning after each dosing subjects will complete fatigue and mood ratings and will perform a brief neuropsychological test battery. They will also undergo actigraphy monitoring for 3 continuous days to examine whether there are subtle lingering effects of the drugs. Blood levels ofproinflammatory cytokines will be obtained at various points before and after drug dosing and the next morning to test the hypothesis that opioid-induced changes in these cytokines are associated with sleep disruption and increased fatigue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: EFFICACY OF ACUPUNCTURE FOR CHRONIC LOW BACK PAIN Principal Investigator & Institution: Cherkin, Daniel C.; Center for Health Studies Seattle, Wa 98101 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 31-JAN-2008 Summary: (provided by applicant): A 5-arm multi-site randomized controlled trial is proposed to clarify the extent to which acupuncture needling can diminish the effect of chronic low back pain on patient functioning and symptoms. Reviews have noted the poor quality of research in this area and urged that scientifically rigorous studies be conducted. Recent higher quality trials suggest acupuncture is a promising treatment for back pain. This study directly addresses methodological shortcomings that have plagued previous studies. Specific aims are to determine, for chronic low back pain, if: 1)
Studies
23
acupuncture is more effective than placebo acupuncture, 2) individualized acupuncture is more effective than standardized acupuncture, 3) acupuncture is more effective when needles are inserted in acupuncture points believed effective for chronic low back pain than when needles are inserted in points considered ineffective for chronic low back pain, 4) acupuncture is more effective than usual medical care alone. A total of 1100 subjects (220 per arm) with low back pain lasting at least 3 months will be recruited from group model HMOs in Seattle, Oakland, and Honolulu. They will be randomized to one of two forms of Traditional Chinese Medical acupuncture needling (individualized or standardized), one of two "control" groups (simulated acupuncture or needling of ineffective points), or to continued usual medical care. Ten treatments will be provided over 7 weeks. The primary outcomes, dysfunction and bothersomeness of low back pain, will be measured at baseline, and after 3, 8, 26 and 52 weeks by telephone interviewers masked to treatment. Analysis of covariance within an intention-to-treat context will be used to analyze the data. Because chronic back pain is a major public health problem and the top reason patients seek acupuncture treatment, a clear, unambiguous assessment is critical for making informed decisions about whether acupuncture should be included as part of conventional care for back pain or covered by insurance. Results of this study will provide the clearest evidence to date about the value of acupuncture needling as a treatment for chronic low back pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFICACY OF ACUPUNCTURE WITH PT FOR KNEE OSTEOARTHRITIS Principal Investigator & Institution: Farrar, John T.; Senior Scholar; Biostatistics and Epidemiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-JUL-2001; Project End 31-MAR-2006 Summary: Acupuncture is an ancient Chinese technique of using a fine needle to stimulate points along theoretical meridians of energy to correct imbalances thought to be responsible for specific disease states. In the United States, acupuncture is often used for the treatment of painful conditions. The 1997 NIH Consensus Conference concluded that there was adequate evidence of efficacy in an acute dental pain model and in nausea. In chronic pain, most studies were too small, poorly designed, poorly executed, or improperly controlled to adequately demonstrate that needle acupuncture worked better than sham acupuncture, placebo, standard medical therapy, or even no treatment. Osteoarthritis (OA) of the knee has been proposed as a good model to test the efficacy of acupuncture in a chronic pain condition because it is an extremely common, well defined, and disabling condition with well established outcome measures for symptoms and functional status. There is clinical trial evidence of efficacy for the standard treatments of acetaminophen and NSAIDs, and exercise physical therapy (EPT), which is usually added when the patient develops functional limitations. One high quality study of acupuncture for knee OA, demonstrated moderate benefit in an unblinded comparison to a usual care control group. As such, a major question remains about whether acupuncture, used in addition to exercise therapy, will provide a clinically meaningful improvement in pain and function. Since pain can be the primary limiting factor in improved exercise capacity, if acupuncture has any efficacy in reducing the pain of knee OA, then the combination with an EPT program should be substantially more effective than EPT alone. Another major concern is that the effect of the acupuncture may be predominantly mediated by non- specific placebo effects rather than the specific effects of the placement of a needle. Another important component of this proposal is our use of a validated blinded placebo needle instead of sham
24
Chronic Pain
acupuncture points. Therefore, the primary goal of this proposal is to use a properly designed randomized blinded clinical trial, using American College of Rheumatology (ACR) criteria and Food and Drug Administration (FDA) recommended outcome measures, to determine whether the addition of acupuncture to standard EPT provides an overall clinically important benefit to patients with symptomatic knee OA compared to placebo acupuncture. As a secondary goal, we will use the clinical trial data to develop prognostic and etiologic models for the patients that are most likely to respond to acupuncture. If a clinically important benefit for acupuncture is found, a broader application of this technique would be justified. However, if the results are negative, then the addition of acupuncture to EPT should be generally curtailed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENDOMETRIOSIS :TRADITIONAL MEDICINE VS HORMONE THERAPY Principal Investigator & Institution: Hammerschlag, Richard; Research Director; None; Oregon College of Oriental Medicine 10525 Se Cherry Blossom Dr Portland, or 97216 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (APPLICANT'S ABSTRACT): Endometriosis is a significant public health problem affecting 10-15% of women of childbearing age, many of whom suffer persistent pelvic pain and infertility. Therapeutic options include surgery and hormone therapy that are often temporarily effective but produce unwanted side-effects. The present proposal, based on case series reports of the effectiveness of Traditional Chinese Medicine (TCM: acupuncture and Chinese herbs) for this condition, aims to evaluate whether TCM is as effective as hormone therapy for alleviating endometriosis-related chronic pain. The study is designed as a prospective trial of 66 women, with laparoscopy-diagnosed endometriosis, randomized to TCM or hormone therapy. Women assigned to TCM will be divided into four sub-groups on the basis of the diagnostic categories of endometriosis recognized by TCM. A pre-established acupuncture protocol and herbal formula specific for each sub-group will be followed. This aspect of the research design permits an important feature of the clinical practice of TCM (matching treatment to sub-group diagnosis) to be adopted in a clinical trial. Women assigned to hormone therapy will be treated with the gonadotropin releasing hormone agonist (GnRHa), nafarelin, chosen for this study on the basis of its clinical trial-established efficacy, ease of patient usage via intranasal spray and milder sideeffect profile relative to other GnRHa's. Pelvic pain symptoms (patient-scored) and signs (physician-scored) will be assessed at baseline, after 12 weeks of treatment, and at 12and 24-week post-treatment follow-up. Pelvic examination scores will be determined by a physician blinded to the treatment group assignments. Side effects, including those of pseudomenopause known to result from GnRHa therapy, will be recorded in both groups at 4-week intervals during the 12-week treatment, and at each follow-up time. A further objective is to make a preliminary assessment of whether diagnostic sub-groups of endometriosis recognized by TCM serve as predictors of differential response to hormone therapy. Data obtained from this study, on treatment effectiveness, side effect profiles, recurrence of symptoms, compliance with therapy and drop-out rates, will be used to design a large-scale clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: EPIDEMIOLOGY OF CHRONIC PELVIC PAIN Principal Investigator & Institution: Clemens, J Quentin.; Assistant Professor; Urology; Northwestern University Office of Sponsored Programs Chicago, Il 60611
Studies
25
Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-AUG-2006 Summary: (Provided by Applicant): The primary aim of this application is to obtain novel information about chronic pelvic pain of bladder origin (CPPBO) in order to determine the magnitude of the problem and its cost to society. This study builds on our ongoing collaborative work with the NIH Chronic Prostatitis Collaborative Clinical Research Study, in which demographics, risk factors, quality of life, and health resource utilization are being evaluated in men with chronic voiding symptoms and pelvic pain. These studies are ongoing, and we will utilize similar methods in men and women in order to obtain consistent data for comparison between the sexes. The specific aims are: 1) to assess the prevalence and incidence of CPPBO. A clinically useful definition of the syndrome will be described, and this definition will be used to assess the prevalence of the syndrome in a large, diverse patient population. Using the same definition, the incidence of new cases will subsequently be determined over a three-year time period; 2) to determine risk factors for the development of CPPBO. A case-control study will be performed using age- and gender-matched controls in order to evaluate for medical conditions and lifestyle factors which are associated with the syndrome; and 3) to evaluate the effect of CPPBO on patient quality of life and health resource utilization. To conduct this study, two populations will be utilized. A database of patients from the Kaiser Permanente Foundation Hospitals in Oregon will be used to assess population prevalence and incidence rates and direct medical costs. Questionnaires will be mailed to a random sample of the Kaiser Permanente patients to obtain detailed information about symptoms and quality of life (QOL). In addition, patients diagnosed with CPPBO at the Northwestern Memorial Faculty Foundation Urology Clinic will undergo a more extensive questionnaire evaluation to analyze medical and lifestyle risk factors for the presence of CPPBO and to obtain additional QOL and health resource utilization information. Answers from the Urology clinic patients will be compared with those of age-and gender-matched controls in a case-control study design. This project will provide novel, population-based epidemiologic information about chronic pelvic pain of bladder origin in both men and women, and will help to further define the public health burden of this extremely common condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FIBROMYALGIA AND TMD IN YOUNG WOMEN-A MULTIRACIAL STUDY Principal Investigator & Institution: Plesh, Octavia; Professor; Preventative and Restorative Dental Sciences; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 25-SEP-1999; Project End 31-AUG-2004 Summary: This investigation will determine the relationship of temporomandibular disorders (TMDs) with fibromyalgia (FM) and factors associated with the two conditions in an established, populations-based cohort (51% black, 49% white) women; and assess racial differences regarding prevalence and the factors explaining this difference. This cohort has been participating for 10 years in the longitudinal National Heart Lung and Blood Institute Growth and Health Study (NGHS) conducted by the University of California, Berkeley and the University of Cincinnati The specific aims are: 1) to assess the prevalence of self-reported, common chronic pains (including TMD and FM) based on questionnaires and to identify potential TMD, FM, and regional chronic pain (RCP) cases and controls; 2) to clinically determine combined body pain and TMD status based on palpating tender points and the distribution of TMD diagnostic types; 3) to compare potential explanatory risk factors (predictors) for these groups and
26
Chronic Pain
determine the temporal relationship between NGHS-collected factors and diagnostic group status; 4) to analyze factors responsible for racial differences. The cohort consists of 1573 women currently 18-19 years old, recruited from west Contra Costa County, CA and the greater Cincinnati area. Longitudinal data collected over 10 years in the NGHS study regarding physical development, (e.g. growth, sexual development, and reproductive health history) and psychosocial development (e.g. coping strategies inventory and family environmental scale) will be assessed as potential risk factors for combined body pain and TMD group status. These longitudinal data collected during the development of this cohort offer a unique opportunity to study multiple risk factors thought to be associated with different types of chronic pain such as FM and TMDs, as they enter the most vulnerable period of life for developing such conditions. Our proposed study will be able to examine the interconnectedness of the longitudinal psychosocial and physiological measures with cross-sectional FM and TMD status, enabling a case-control design to draw conclusions like a longitudinal study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FOREBRAIN MECHANISMS IN CHRONIC NON-NEUROPATHIC PAIN Principal Investigator & Institution: Casey, Kenneth L.; Professor; Neurology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Psychophysical studies have shown that patients with fibromyalgia (FM) have cutaneous heat and pressure thresholds that are lower and ratings of these stimuli that are higher than normal. Patients with the chronic pain of arthritis (CPA) have similar, but less severe, hypersensitivity to cutaneous heat and pressure stimuli. These abnormalities may reflect an amplification of forebrain nociceptive processing due to continual nociceptive input (CPA), or primary adaptive changes in CNS nociceptive processing (FM). We will obtain psychophysical measurements of the thresholds and perceived intensities and unpleasantness of cutaneous heat and somatic pressure stimuli in all subjects. We will use H215O positron emission tomography (PET) to test the overall hypothesis that FM and CPA patients have correspondingly larger stimulusevoked increases in regional cerebral blood flow (rCBF) within bilateral volumes of interest (VOI; thalamus, insula, and the sensorimotor (S1/M1), S2, anterior cingulate, and premotor (B6) cortices) than normal subjects. Because FM occurs primarily in women, we will study two groups of right-handed female patients: 20 with FM and 20 with CPA, and compare their rCBF responses to those of 20 normal women within the same age range (20-50 years). Patients will rate their clinical pain at or above 4 on a visual analog scale of pain (VAS; 0-10) and will complete a short-form McGill Pain Questionnaire (VAS, MPQ). Standard VOI will be developed in normal subjects from peak rCBF increases within the above structures in response to heat stimuli applied at 35EC, heat pain threshold (HPT), heat pain tolerance (Hptol), and at 3 additional intensities anchored symmetrically around HPT and below Hptol. These standard VOI and stimulus intensities will be used to determine the correlation between rCBF increases and applied stimulus intensity and perceived unpleasantness, as estimated with a VAS, in normal subjects and in patients with FM or CPA who have not been taking opioid analgesic or psychoactive medication for one month. We predict that the psychophysical responses, and the rCBF responses within one or more VOI will be larger in FM and CPA patients than in normal subjects. These same studies will be performed again after all patients have been taking nortriptyline (NT) and/or physical therapy (PT) for approximately one year. Normal subjects will take NT for 3 weeks
Studies
27
before the second PET scan (1 year later). We predict that both patient groups, but not normal subjects, will show clinical pain scores, stimulus-evoked psychophysical responses, and rCBF responses, in one or more VOI, that are less than those obtained before NT or PT treatment. We will also examine differences between FM and CPA patients. Support for the overall and correlative hypotheses will constitute evidence that, in the absence of peripheral causes, the pain experienced by FM and CPA patients is due, at least in part, to abnormal central nociceptive processing mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL CONSEQUENCES OF RECURRENT PAIN IN CHILDREN Principal Investigator & Institution: Palermo, Tonya M.; Assistant Professor; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 10-FEB-2000; Project End 31-JAN-2005 Summary: The candidate is a postdoctoral fellow in pediatric psychology who is advancing to a junior faculty position. This award is expected to help transition the focus of the candidate's research and to provide additional training in chronic and recurrent pain in children, in particular, the associated functional morbidity. The candidate's career goals are to develop an independent research career related to identification and prevention of pain-related functional consequences and children. Specific objectives are to: 1) broaden understanding of the functional impact of chronic and recurrent pain in children through consideration of multiple child and family specific domains, and 2) to use psychosocial family assessment data to develop interventions to prevent or limit functional consequences of pain in children. The candidate proposes a five-year training program with faculty mentors from a strong pediatric research department. her sponsor is a very experienced pediatric psychology researcher whose work has focused on identifying factors that enhanced or disrupt the psychosocial adaptation of children with chronic illness. Co-sponsors and mentors represent subspecialty divisions that are directly relevant to the research and career development plan. The career development plan describes activities focused on enhanced knowledge of research-related approaches to the management of chronic and recurrent pain and pain-related disability in children through coursework, independent study, and clinic observations. Other activities in the plan include research training in statistical methods supervised experienced in preparation of grant proposals for individual research support, and training in the responsible conduct of research. The candidate's proposed research involves three projects. Study 1 is a baseline assessment of pain- related functional consequences and potential family moderators of impairment in children with sickle cell disease, juvenile chronic arthritis, and migraine headaches. Study 2 is a follow-up of this sample at 12 months to provide as yet unavailable information on the functional impact of chronic and recurrent pain over time. Study 3 is a pilot study to develop and evaluate family-centered interventions to reduce functional consequences of recurrent and chronic pain in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: FUNCTIONAL IMPACT OF PENS FOR 65+ CHRONIC LOW BACK PAIN Principal Investigator & Institution: Weiner, Debra K.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2007
28
Chronic Pain
Summary: (provided by applicant): Chronic low back pain (CLBP) plagues greater than 6 million community dwelling older adults, and causes physical and psychosocial dysfunction as well as increased utilization of health care resources. While the mainstay of treatment for these individuals consists of non-opioid analgesics and physical therapy (PT), frail older adults with unrelieved symptoms have limited therapeutic alternatives. Opioid analgesics and surgical treatment may be inapplicable to those with prohibitive physical or cognitive comorbidities. Many individuals with chronic musculoskeletal pain seek out complementary and alternative treatments, although most have not been subjected to rigorous scientific investigation. Acupuncture is among the most commonly employed of these modalities. The purpose of this investigation is to explore the utility of percutaneous electrical nerve stimulation (PENS), a neuroanatomically guided form of electroacupuncture, as a safe non-pharmacologic analgesic alternative for the older adult with CLBP. In order to optimize physical performance and diminish disability, the value of a general conditioning and aerobic exercise (GCAE) program with and without PENS will also be studied. A randomized controlled clinical trial will be performed. Two hundred community dwelling older adults equal to or > age 65 with CLBP will receive either (1) PENS alone, (2) sham PENS alone, (3) PENS + GCAE, or (4) sham PENS + GCAE, twice a week for 6 weeks. All outcome measures will be collected pretreatment, at the completion of the 6 weeks protocol, and 6 months later. Primary outcome measures include pain intensity (short form McGill Pain Questionnaire) and pain-related disability (Roland Disability Scale). Because chronic pain is a complex, multidimensional experience, important secondary outcome measures will also be collected that assess key aspects of (1) physical function (self-reported and performancebased), (2) psychosocial function (mood, self-efficacy, self-rated health, cognitive coping, fear, sleep), and (3) health care utilization. This study represents the first wellcontrolled, comprehensive examination of an alternative medicine intervention for CLBP in older adults. If effective, this trial could lead to improved quality of life for millions of suffering older Americans, and by diminishing pain intensity and the use of toxic analgesic regimens, lead to substantial cost savings by decreasing health care utilization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR PAIN Principal Investigator & Institution: Fink, David J.; Professor; Neurology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Pain is a subjective experience with affective and cognitive components, an "unpleasant sensory and emotional experience associated with actual or potential tissue damage that serves an essential role in alerting an individual to potentially harmful stimuli in the environment". But chronic pain, often disabling and refractory to treatment, represents a difficult medical problem with enormous societal impact. Herpes simplex virus (HSV) naturally targets with high efficiency to neurons of the dorsal root ganglion (DRG) from peripheral inoculation. We have demonstrated that HSV based vectors can be used to transduce neurons of the DRG to achieve an antinociceptive effect in models of inflammatory pain, neuropathic pain, and pain resulting from tumor in bone. The effect is local, synergistic with morphine, and persists despite tolerance to morphine. The preclinical data for this novel approach to the treatment of pain is compelling. In response to the RFA, we propose a series of studies to investigate the hypothesis that HSV-mediated gene transfer to the DRG may be used to treat chronic pain. These studies are designed to overcome the barriers that stand
Studies
29
between preclinical proof-of-principle experiments and the development of a treatment for the human disease, and to create novel vectors to enhance gene therapy for specific types of pain. Five specific aims are outlined. Specific Aim 1. To define the duration and dose-response characteristics of the vector-mediated analgesic effect. Specific Aim 2. To construct a vector with a regulatable "switch" to control vector-mediated enkephalin expression in vivo. Specific Aim 3. To test the effect of prior immunity on vector transduction, the potential of the recombinant vector to reactivate latent virus, and to study the level and kinetics of the anti-nociceptive response following repeated vector re-inoculation. Specific Aim 4. To systematically evaluate biodistribution and biosafety of the recombinant enkephalin expressing vector in rodents. Specific Aim 5. To create and test novel HSV-based vectors in models of neuropathic, inflammatory, and cancer pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF OPIOID INDUCED HYPERALGESIA Principal Investigator & Institution: Clark, David J.; Anesthesia; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Opioids constitute the single most useful and commonly used class of analgesics for pain of moderate or severe intensity. The use of opioids for chronic pain has grown very rapidly in recent years, yet we have a poor understanding of some of the limitations of this form of therapy. Recently it has been reported both from work in humans and animal models that the chronic administration of opioids can lead to a state of hyperalgesia termed opioid-induced hyperalgesia (OIH). This phenomenon may limit the utility of opioids used for the treatment of chronic pain. Our understanding of OIH to this point has relied primarily on the use of pharmacological tools and has grown to include data supporting roles for monoxide signaling systems like heme oxygenase and nitric oxide synthase, the NMDA receptor, dynorphin and alterations in various nociceptive and regulatory pathways. We lack, however, data concerning the genetics of susceptibility to OIH. Where employed by other investigators genetic studies involving mice have provided unique incites into the mechanisms of nociception and analgesia. We propose to employ a genomic mapping strategy in which behavioral observations concerning the susceptibility of several strains of mice to the development of OIH after the repeated administration of morphine are coupled with a recently developed computational algorithm and a single nucleotide polymorphism (SNP) database to identify segments of the genome likely to be involved in susceptibility to OIH. In addition, we will be able to collect data concerning the basal sensitivity of these strains to morphine, as well as the extent of tolerance developed and the degree of physical dependence induced by repeated administration of this opioid. Thus a second dimension of the studies will be to make mechanistic comparisons between the phenomena of OIH, morphine induced analgesia, tolerance and physical dependence. These data will be collected over the two years of support requested (stage 1) and will form the foundation for stage 2 studies in which specific experiments will be designed to further refine our map and to examine the roles of genes chosen from the high probability mapping regions in the development of OIH. Thus our overall goal is to bring a unique and complimentary approach to the ongoing studies of OIH by using genomics to objectively identify genes involved in this phenomenon. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
30
Chronic Pain
•
Project Title: GLUTAMATE INFLAMMATION
IN
PERIPHERAL
AFFERENTS
DURING
Principal Investigator & Institution: Miller, Kenneth E.; Anatomy and Cell Biology; College of Osteopathic Med/Ok State Univ of Oklahoma State University Tulsa, Ok 74107 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Pain is a debilitating complication during chronic inflammation, such as arthritis, and difficult to treat for long periods of time. We hypothesize that elevated glutamate release from sensory nerves is responsible, in part, for the enhanced pain sensitivities of chronic inflammation. We have discovered in a rat model of chronic inflammation that sensory nerves in skin/joints produce large amounts of glutamate and its synthetic enzyme, glutaminase. Chronic inflammation causes increased production of glutaminase in the neuronal cell bodies of the sensory nerves that is shipped to the skin and joints causing increased levels of glutamate. A chronic increase in the production and release of glutamate can stimulate glutamate receptors on sensory nerves to produce painful sensations. For the current proposal, we hypothesize that elevated levels of glutamate cause 1exaggerated painful responses during chronic inflammation. In addition, preliminary data indicate that nerve growth factor (NGF) as a retrograde signal and zeta-crystallin:quinone oxidoreductase (ZC) as a stabilizer of glutaminase mRNA are important for this chronic alteration in glutamate metabolism. We postulate, therefore, that NGF and ZC are responsible for altering glutaminase levels in primary sensory neurons during chronic inflammation. The following specific aims are presented: 1. Our hypothesis predicts that inhibition of glutaminase will reduce nociceptive responses and elevated glutamate levels during chronic inflammation. A glutaminase inhibitor will be administered to sensory neurons during chronic inflammation. 2. Our hypothesis predicts that glutaminase production in sensory neurons during chronic inflammation is regulated by ZC. A ZC inhibitor will be given to sensory neurons during the development of chronic inflammation. 3. Our hypothesis predicts that glutamate metabolism in sensory neurons can be modified by NGF. NGF administration to naive rats and NGF inhibition during chronic inflammation will be evaluated. Behavioral tests will determine responses to pressure and temperature. Biochemical & immunohistochemical analyses will evaluate alterations in glutamate and GT enzyme levels in the sensory cell bodies and sensory nerves. Results from these studies will give insight into the role of peripheral glutamate on nociceptive responses during inflammatory chronic pain. These results may be beneficial in the development of novel therapies for patients with intractable pain by addressing the regulation of glutamate in peripheral tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTAMATE RECEPTORS AND CHRONIC CENTRAL PAIN IN SCI Principal Investigator & Institution: Tan, Huaiyu; Anatomy and Neurosciences; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Spinal cord injury (SCI) results in severe somatosensory and locomotor impairments. The project will investigate the role of glutamate receptors in chronic pand pharmacological techniques. The rats used will receive a spinal contusion injury, which best resembles blunt impact trauma in human SCI. Mechanical and thermal allodynia will be tested behaviorally. Extracellular recordings of spinal cord neurons in anesthetized rats will be used to test the following
Studies
31
hypotheses: 1) Spinal cord injury produces central sensitization of dorsal horn neurons, which can be measured by electrophysiological techniques. 2) Increased activation state of ionotropic (NMDA and non-NMDA) glutamate receptors following SCI contributes to central sensitization and thus to CCP. The Specific Aims are: 1) To analyze SCIevoked changes of responsiveness of nociceptive spinal dorsal horn neurons to peripheral mechanical and thermal stimuli. 2) To determine the contribution of ionotropic glutamate receptors in SCI-evoked changes in nociceptive dorsal horn neurons. These results will provide important new information on the electrophysiological and pharmacological mechanisms of chronic central pain after SCI. They will also provide valuable insight into the potential therapeutic value of ionotropic glutamate receptors as targets for pain relief after SCI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GONADAL STEROID HORMONAL REGULATION OF PESISTENT PAIN Principal Investigator & Institution: Ren, Ke; Associate Professor; Oral Surgery; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: Chronic or persistent pain affects millions of adults each year with costs in lost work days, medical treatment and the reduction in the quality of life in the range of billions of dollars. Many of these conditions are gender-related. Women exhibit a higher prevalence of temporomandibular disorders, neuropathic pain, fibromyalgia, migraine headaches and some forms of arthritis. Furthermore, variations in hormonal levels associated with menstrual cycle, menopause, pregnancy and lactation influence pain levels. The purpose of this study is to evaluate the effects of progesterone and progesterone in combination with estrogen on the hyperalgesia and neuronal hyperexcitability associated with a rat model of persistent pain and inflammation. Our major hypothesis is that endogenous reproductive hormones can suppress persistent pain by their influence on a cascade of molecular, biochemical and physiological events at the spinal level involving inhibitory and excitatory amino acids and their receptors, and opioid peptides and their receptors. We will investigate the effects of these hormones on behavioral hyperalgesia, spinal cord neurons, modulation of GABA receptors, expression of opioid receptors and opioid peptides, and NMDA receptor function. Specific Aim 1 will characterize the changes in behavioral inflammatory hyperalgesia produced by progesterone, in lactating females, ovariectomized females with hormone replacement, and castrated males. Specific Aim 2 will determine the effects of progesterone on the development and maintenance of behavioral hyperalgesia, as well as the possible target sites of the antihyperalgesic effects in peripheral tissue, the spinal cord and the brain. Specific Aim 3 will determine that progesterone's antihyperalgesic effects are mediated, in part, via modulation of GABAA receptor activation. Specific Aim 4 will test the hypothesis that progesterone's antihyperalgesic effects are opioid-mediated, in part, at the level of the spinal cord. Specific Aim 5 will examine progesterone effects on NMDA receptor function and changes in NMDA receptor subunit gene expression following inflammation and hyperalgesia. In summary, we propose to elucidate the influence of reproductive hormones on mechanisms of persistent pain in a rat model that mimics human chronic pain conditions known to exhibit cyclical or pregnancy-related variations. The findings will be important for the development of new approaches to the management of these conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
32
Chronic Pain
•
Project Title: IMPROVING CANCER PAIN MANAGEMENT IN THE HOME Principal Investigator & Institution: Vallerand, April H.; None; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 06-SEP-2000; Project End 31-AUG-2003 Summary: Dr. Vallerand has had a long-standing interest in symptom management, particularly pain in patients facing life threatening diseases. Her program of research focuses on the maintenance and improvement of functional status in patients with chronic pain. The proposed study extends Dr. Vallerand's previous work into the community setting. The design of the study allows her to develop new research skills in working with a complex design and a large data set. The role of perceived control over pain is intriguing to this investigator. Information from this study will help determine the importance of this concept to nurses, patients, and caregivers. Developing interventions to increase the perception of control, such as allowing the patient to choose from the many treatment modalities available for chronic pain, may increase this perception and enhance adherence to the treatment plan. The overall goal of this study is to determine the effect of programs of structured educational interventions directed at nurses, and at patients and their caregivers, on the management of pain and opioidrelated symptoms in home care patients with cancer. The investigator has considerable experience educating nurses about the pharmacologic management of pain and promoting optimal functional status in patients with chronic pain. Although a number of educational programs have been presented regarding pain management, mastery of this content and its utilization in practice by nurses has not been achieved. This study will test the effects of a two-session educational intervention administered to nurses, combined with a patient/caregiver educational intervention in a mixed methods 2 x 2 (nurse intervention x patient/caregiver intervention) multilevel longitudinal design. The effects of the nurse intervention, the patient/caregiver intervention, and the joint effects of both interventions on the nurse's, patient's, and caregiver's perceived control over pain and on patient outcomes, including pain, symptom distress, and analgesic usage, will be measured. Dr. Vallerand is an Assistant Professor in the Area of Adult Health and Administration. Dr. Stephen Cavanagh is the Assistant Dean for the Area. Dr. Ada Jacox, Associate Dean for the College of Nursing will assist the candidate in her research career development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: INTEGRATIVE PAIN MEDICINE Principal Investigator & Institution: Kronenberg, Fredi; Rehabilitation Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Chronic pain disables almost 50 million Americans, and is one of the most under-treated conditions in modern health care. The elderly are most affected by pain, and often take multiple medications that have unexamined potential for interaction. Thus, as our population ages, non-pharmaceutical approaches to pain management will be of great value to internists, geriatricians, reheumatologists, oncologist and all those involved with older patients. Recent studies have also demonstrated that the primary reason people use complementary and alternative medicine (CAM) is for pain. Yet, very little is taught about conventional pain medicine at either the undergraduate or post-graduate levels, and even less about how common CAM therapies can appropriately be woven into the clinical practice of modern pain medicine. While there are a few isolated and generally short programs on CAM for pain
Studies
33
offered at national pain meetings, there has not been a complete and comprehensive conference on the state-of-the-science of pain medicine, focusing on an integrated approach to pain medicine. We propose to meet this need through a new conference: "Integrative Pain Medicine." The purpose of this unique and much needed program will be to give an overview of the evidence base for pain medicine in an integrative model that combines current conventional medicines with the best of CAM therapies. The presenters will be asked to critically review the current scientific literature justifying the various therapies for pain, and to clearly describe the state-of-the-science. The audience will be practicing clinicians who deal with pain. The Specific Aims of the conference are to: Describe the fundamentals of modern pain medicine; Describe some of the best conventional and CAM therapies for use in pain management; Present research data to support conventional and CAM therapies for pain; Enable clinicians to know how to identify and evaluate competent CAM practioners and have a sense of how to interact with them; and Present information on the practical integration of useful CAM therapies into the treatment of pain patients with and without cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRACELLULAR DORSAL HORN MECHANISMS OF PAIN ENCODING Principal Investigator & Institution: Dougherty, Patrick M.; Associate Professor; Anesthesiology/Crit Care; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: Hundreds of thousands of patients each year develop chronic pain and hyperalgesia. Many of these conditions remain poorly treated due to our limited understanding of functional organization in the spinal dorsal horn. Though extracellular studies in intact animals are well suited for defining the complex physiologic systems underlying pain signaling, intracellular studies in reduced preparations are best suited for determination of cellular processes. As a means to advance our understanding of spinal mechanisms of pain encoding we propose that these approaches should be combined. To this end we have adapted whole-cellpatch clamp intracellular recording for use in an intact anesthetized preparation of the rodent dorsal horn. Initial studies with this approach have already revealed new properties of neurons in the superficial spinal lamina. For example, biophysical parameters of spinal neurons were correlated to their profile of responses to peripheral stimuli. Additionally, a novel population of silent dorsal horn cells has been identified with latent responses to cutaneous stimuli that can be activated by membrane depolarization. Thus, in viva whole cell patch clamp in intact animals represents an exciting new approach for the study of cellular mechanisms of sensory integration in the dorsal horn. We propose here to extend our preliminary studies in cells of the superficial lamina, to expand the study to include neurons in deeper spinal lamina, and importantly, to determine the biophysical differences between projection and non-projection neurons. The studies outlined in this application will define the mechanisms by which the biophysical properties of cells influence both their action potential and subliminal excitatory and inhibitory responses to natural cutaneous stimuli. Additionally we will define the ionic bases of the biophysical differences among cells of differing functional classification. Knowledge of this kind is a key to advancing our knowledge of the cellular mechanisms of dorsal horn sensory integration and so will result in a better understanding and improved treatment of acute and chronic pain as well as further our understanding of conscious perception of somatic sensation.
34
Chronic Pain
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MANAGEMENT OF CHRONIC PAIN IN REHABILITATION MEDICINE Principal Investigator & Institution: Jensen, Mark P.; Professor; Rehabilitation Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 25-AUG-1996; Project End 31-MAY-2007 Summary: (provided by applicant): This application requests continuation of the program project entitled "Management of Chronic Pain In Rehabilitation." The overall goal is to conduct multidisciplinary research aimed at understanding the nature, development, course, and appropriate care of chronic pain as a secondary condition in persons with disabilities. The project will continue to focus on using survey research to understand the frequency and severity of pain in persons with disabilities, and to continue testing the efficacy of treatments designed to decrease pain and its impact. Project by Jensen will survey 3,730 adults and children with disabilities to: (1) further our understanding of pain as a secondary condition in persons with disabilities, (2) perform a prospective, longitudinal study to clarify the natural course of pain in adults and children with disabilities, and (3) further develop a biopsychosocial model of chronic pain as it applies to persons with disabilities. Project by Ehde will evaluate the efficacy of cognitive restructuring, relative to an education/attention control condition, in the management of chronic pain in persons with disabilities, and determine the causal impact of pain cognitions (specifically, catastrophizing cognitions) on functioning in persons with disability-related chronic pain. Project by Engel includes a randomized clinical trial and a series of single-subject studies designed to test the efficacy of relaxation training for reducing pain in youth with disability-related pain, and to test three hypothesized mechanisms for the efficacy of relaxation training for reducing pain in youth. A Scientific Core will provide scientific direction, project coordination, data collection and management, statistical support, and shared scientific expertise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MAXIMIZING FIBROMYALGIA.
BENEFICIAL
EXERCISE
EFFECTS
IN
Principal Investigator & Institution: Jones, Kim D.; Primary Care Nursing; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2006 Summary: (provided by applicant) Fibromyalgia (FM) is a common, costly and debilitating chronic pain syndrome diagnosed in nearly 6 million Americans, 90% of whom are women. Conservative estimates place direct and indirect costs of FM at $700 million annually. By definition, people with FM have chronic widespread pain and specified tender point areas. Other symptoms associated with FM include disrupted sleep, fatigue, decreased cognition, visceral and other pain syndromes, neurological symptoms, post-exertion muscle pain and exercise intolerance. The majority of people with FM are known to be aerobically unfit, have poor muscle strength and limited flexibility. Deconditioned muscle is theoretically more prone to muscle microtrauma, which causes localized pain and triggers widespread pain through disordered central nervous system processing (i.e., central sensitization). A negative cycle of deconditioning occurs in FM in large part due to exercise-induced pain that limits exercise tolerance. Dysfunction of the hypothalamic-somatotropic axis, specifically growth hormone (GH)/insulin-like growth factor-one (IGF-1), may also contribute to exercise
Studies
35
induced pain and exercise intolerance in FM, due to the critical role of GH/IGF-1 in muscle homeostasis and repair following exercise. Over the past 25 years, the broad research theme of the Oregon Health and Science University's (OHSU) Fibromyalgia Research and Treatment Team has been investigating pain in fibromyalgia with an emphasis on exercise and pharmacological therapies. We recently documented GH/IGF-1 dysfunction in persons with FM at rest, and in response to exercise. We also pharmacologically altered the GH/IGF-1 axis in women with FM, with resultant improvements in pain and exercise tolerance by self-report. The focus of the proposed study is to test the effects of exercise training in women with FM whose GH profiles have been experimentally manipulated with low dose pyridostigmine bromide (Mestinon). To fully investigate the effects of exercise training and pyridostigmine bromide, a 2 x 2 x 2 (exercise x drug x time) design will be used. We propose a randomized clinical trial in which four groups of participants are observed over time (placebo only, pyridostigmine bromide only, exercise + placebo and exercise + pyridostigmine bromide). We will test the effects of the exercise and drug independent variables, alone and in combination, on the outcome variables of 1) pain and 2) FM associated symptoms and impact, cognition and quality of life. The specific aims of this study are to: Test the effects of a 6-month, 3-times-weekly exercise training program plus 3-times-daily 60 mg pyridostigmine bromide on pain, the primary and defining symptom of FM; and test the effects of a 6-month, 3-times-weekly exercise training program plus 3-times-daily 60 mg pyridostigmine bromide on FM-associated symptoms and impact, cognition, and quality of life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF CHRONIC VISCERAL HYPERALGESIA Principal Investigator & Institution: Al-Chaer, Elie D.; Professor; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 05-APR-2001; Project End 31-MAR-2005 Summary: Visceral hyperalgesia is a hallmark of the irritable bowel syndrome (IBS), an extremely common disorder, affecting up to 15 percent of the US population with a major socioeconomic impact. Our understanding of the hyperalgesia in functional pain syndromes such as lBS lags behind our knowledge of the mechanisms of other types of visceral pain that are mechanically-induced or caused by inflammatory reactions mainly because of the lack of a valid animal model. Recently, it was shown that functional abdominal pain can be modeled in animals. Colon irritation (CI) in neonatal but not adult rats, can cause a long lasting visceral hyperalgesia that persists long after the initial injury has resolved. In this study, the central hypothesis is that persistent colonic hyperalgesia, residual to neonatal colon irritation, is associated with central neural sensitization maintained by an interactive exchange of information between the spinal cord and thalamus. HYPOTHESIS 1: There exists a postnatal window of time when minimal colon irritation can induce permanent changes in the nervous system that leads to chronic visceral hyperalgesia. SPECIFIC AIM] will define this window of time in postnatal development using noxious mechanical distension or chemical irritation of the colon to cause chronic visceral hyperalgesia. HYPOTHESIS 2: The persistent visceral hyperalgesia residual to neonatal CI is maintained by central plastic changes in neuronal sensitivity. SPECIFIC AIM 2 will demonstrate with immunocytochemistry and electrophysiology, that the chronic visceral hyperalgesia is associated with neuronal sensitization in the spinal cord and the thalamus. HYPOTHESIS 3: The sensitization is maintained in part by neuronal mechanisms involving glutamatergic and peptidergic processes. SPECIFIC AIM 3 will determine if blockade of glutamate or neurokinin
36
Chronic Pain
receptors by specific antagonists will reduce the central sensitization. HYPOTHESIS 4: The central sensitization is maintained by an intact dorsal column (DC) participating in a feed-forward dynamic exchange of information between the dorsal horn of the spinal cord and the thalamus. SPECIFIC AIM 4 will demonstrate, using electrophysiology and behavior studies, that the sensitization is mediated by an intact DC-thalamus communication that maintains thalamic sensitization and amplifies spinal neuronal sensitivity via descending pathways. The long-term objective of the proposed study is to define the neurophysiological correlates of chronic visceral hyperalgesia and hence to identify novel therapeutic targets for the relief of pain in patients with functional bowel disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATION OF G PROTEIN COUPLED RECEPTOR FUNCTION Principal Investigator & Institution: Childers, Steven R.; Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Opioid agonists like morphine, codeine and meperidine remain the most commonly used and effective treatment for chronic pain conditions. Despite the fact that chronic opioid treatment can produce high levels of tolerance and physical dependence. Mechanisms of tolerance and dependence for in brain are not well understood, but it is clear that chronic opioid treatment produces significant receptor desensitization in specific brain regions. Moreover, pain itself, as well as concurrent treatment with drugs like adenosine and alpha2- adrenergic agonists, alter the sensitivity of patients to opioid treatment. Opioid receptors (including mu, delta and kappa types), as well as adenosine A1 and alpha2-adrenergic receptors, are G-proteincoupled receptors, and their ability to activate signal transduction systems can be determined by the ability of agonists to stimulate [35S]GTPgammaS binding in both membranes and section autoradiography. This project will examine regulation of several receptor/G-protein interactions in rat spinal cord, using models of drug treatment, selfadministration and chronic pain developed by other Center components. First, after determining the acute efficacies of opioid and adenosine A1 agonists in activating Gproteins in spinal cord, the ability of chronic drug exposure to produce receptor desensitization will be examined in both spinal cord membranes and by autoradiography. These treatments will include chronic intrathecal opioid administration to desensitize opioid receptor-activated G-proteins, and chronic intrathecal administration of adenosine and clonidine to desensitize agonist-stimulated incorporation of [32P]AAGTP into specific G-protein subunits. Second, various receptoractivated G-protein activities will be determined in both brains ans spinal cords from spinal nerve ligated rats to determine whether chronic pain and hypersensitivity affect receptor/G-protein coupling. These studies will also determine how chronic pain states modulate basal levels and activities of G-proteins in spinal cord. Third, the ability of NMDA antagonists and protein kinase C inhibitors to modulate receptor desensitization will be tested after chronic intrathecal administration of drugs. Information from this project will help design studies in the Clinical Core to test the use of opioid agonists of differing efficacies in treating chronic pain. Moreover, these studies will provide information to minimize tolerance in long-term drug treatment of chronic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
37
Project Title: MOLECULAR TARGETING OF THE VANILLOID-1 RECEPTOR Principal Investigator & Institution: Neubert, John K.; Orthodontics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The goal of this proposal is to provide the Principal Investigator, John K. Neubert, DDS, PhD, with the opportunity to develop as an independent translational pain researcher. Dr. Neubert has completed a dental residency in orofacial pain management and a PhD in Oral Biology at UCLA and is finishing a clinical research fellowship at the NIH. Additional experience in fundamental molecular and cellular biology is required to provide the principal investigator with the requisite skills needed for this translational research. This experience will be acquired during the Scholar Development Phase and will complement the Principal Investigator's prior in vivo physiological and clinical pain research experiences. This phase will be supervised by Dr. Michael Iadarola at the NIH, who has over 20 years of experience and continues to excel in the areas of molecular and cellular pain biology. Dr. Neubert will receive full institutional support during the Scholar Development Phase from the NIDCR, NIH, including use of facilities, equipment, and support staff. The Faculty Transition Phase will be critical for the principal investigator to become an innovative and independent researcher. Chronic pain continues to affect a countless number of individuals and costs society billions of dollars each year. The vanilloid-1 receptor (VR1) provides an excellent target for analgesia due to its prominent role in inflammation and hyperalgesia. The long-range goal is to investigate the peripheral actions of VR1. The objective is to elucidate the role of VR1 through specific ultrapotent agonists and antagonists designed to induce or block neuronal cells expressing this receptor in vitro, and to evaluate these agents in vivo. The central hypothesis of the proposed research is that peripheral VR1 activity is necessary to effectively transduce painful stimuli. Three Specific Aims will be investigated: Aim #1, Pharmacologically characterize the function of the VR1 ionophore; Aim #2, Evaluate the analgesic efficacy of vanilloid receptor agonists in models of acute pain; Aim #3, Clinically evaluate the analgesic efficacy of vanilloid receptor agonists for acute and chronic orofacial pain conditions. These aims will be tested by an experimental approach using VRl-transfected cell lines and evaluating their inhibition by chemical compounds screened from combinatorial libraries. Additionally, peripheral application of the potent VR1 agonist, resiniferatoxin (RTX), will be tested in vivo through a number of behavioral and histological assessments to determine if vanilloids are effective in blocking pain. Lastly, RTX will be evaluated for analgesic efficacy in human models of acute and chronic pain. Completion of the proposed studies is expected to provide a better understanding of the mechanisms responsible for contributing to clinical pain, thus leading to development of mechanistically-derived therapies. These outcomes are expected to have significant positive effects on a wide spectrum of pain relating to tissue damage and injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: NEURAL MECHANISMS OF ANESTHESIA Principal Investigator & Institution: Kendig, Joan J.; Professor; Anesthesia; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-MAY-1978; Project End 31-AUG-2004 Summary: Spinal cord synaptic plasticity is increasingly recognized as important in pain and analgesia. Synaptic plasticity may also be important in drug-induced tolerance and
38
Chronic Pain
withdrawal. In the past funding period we have obtained evidence that the spinal potency of both opioid analgesics and ethanol is negatively modulated by the development of acute neuronal tolerance, and that withdrawal hyperresponsiveness is associated with these agents. In addition we have partially characterized a form of stimulus-induced long-term potentiation (LTP) in spinal cord that may serve as a model for the central sensitization associated with pathologic pain states. Although the cellular loci and detailed mechanisms for these forms of spinal plasticity almost certainly differ, there may be a broadly common mechanism of receptor phosphorylation mediated by protein kinase C. We will test the overall hypothesis that opioids, ethanol, volatile general anesthetic agents and high frequency nociceptive afferent stimulation induce spinal hyperexcitability by altering the phosphorylation state of one or more critical receptor/ion channel complexes in spinal cord neurons, with particular attention to calcium-permeable ion channels. There are four Specific Aims, each linked to mechanistic hypotheses. 1. Clinical inhalation anesthetic agents, like ethanol, induce rapid acute neuronal tolerance and withdrawal in spinal cord motor neurons. Tolerance and/or withdrawal to ethanol and volatile anesthetics are mediated by protein kinase C and depend on increased calcium influx. 2. Mu opiod analgesics induce rapid acute tolerance as well as withdrawal in spinal cord by an action involving protein kinase C leading to increased calcium influx via NMDA receptors. 3. Spinal LTP shares a common mechanism with acute opioid tolerance and withdrawal. 4. Synergistic actions between several classes of agents are due to block of rapid acute tolerance. All experiments will be carried out in vitro in spinal cords from young rats, using population ventral root responses evoked by dorsal root stimulation in whole cords and patch recording from visually identified motor neurons in spinal cord slices. The results will shed light on the mechanistic basis for anesthetic and analgesic drug potency. Clinically tolerance to opioid analgesics is a major problem in the treatment of chronic pain. Rapid acute tolerance is becoming recognized as a major determinant of sensitivity to ethanol. Tolerance and withdrawal are not yet accepted for most inhalation anesthetic agents, and if demonstrated will cause a change in the way the clinical and theoretical properties of these agents are considered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL MECHANISMS OF PAIN AND HYPERALGESIA Principal Investigator & Institution: Levine, Jon D.; Professor of Medicine; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUL-1985; Project End 31-MAR-2003 Summary: (adapted from the applicant's abstract) Inflammatory pain is a very common clinical phenomenon that causes great individual suffering and expense to society. Some of the most severe forms of pain, particularly chronic inflammatory pains, are partly or wholly intractable to currently available therapies. The investigators have shown that the cAMP/PKA second messenger pathway plays a major role in hyperalgesia induced by prostaglandin E2 (PGE2) and recently that nitric oxide (NO) also contributes via a guanylyl cyclase-independent mechanism. They now propose to study the cellular mechanism(s) underlying an additional novel action of NO, guanylyl cyclase-dependent hyperalgesia. They will also investigate the role of PKCepsilon in hyperalgesia and nociceptor sensitization produced by other inflammatory mediators. The investigators will also study mechanisms of mechanical transduction in nociceptors. They have recently been able to demonstrate a mechanically-induced whole cell current in cultured dorsal root ganglion neurons. They propose to fully characterize this current in order to establish an in vitro electrophysiological model for the study of nociception of
Studies
39
mechanical stimuli. The investigators will also investigate changes in second messenger pathways involved in chronic hyperalgesia, focusing on a novel phenomenon they recently discovered in which the hyperalgesic response to an inflammatory mediator is enhanced for a period of weeks following recovery from the inflammatory hyperalgesic state. These experiments should provide significant novel information about mechanisms of inflammatory pain and hyperalgesia and cellular mechanisms of mechanical transduction in primary afferent neurons that may be important in chronic pain states in humans. These investigations should yield insights into potential pharmacological targets for the treatment of chronic inflammatory pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURITE DENSITY IN SKIN AS A MARKER FOR NEUROPATHIC PAIN Principal Investigator & Institution: Oaklander, Anne L.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Chronic pain has been recognized as an underserved area of medicine. Clinical care and research are hampered by the lack of objective correlates for the subjective complaint of pain. This is especially a problem for neuropathic pain patients, where the pain is caused by malfunction of the pain-sensing neurons, rather than injury to the area where the pain is felt. In this translational project we will evaluate two types of objective evidence of neural damage to see whether they correlate with the complaint of pain. We will investigate the usefulness of these methods in adults with one of two common neuropathic pain conditions, postherpetic neuralgia (PHN) after shingles (herpes zoster), or painful neuropathy in the lower legs from diabetes mellitus, and in rat models of these conditions. Data from individuals with and without pain will be compared. We will evaluate the usefulness of tests of specific sensory functions, using standardized quantitative sensory stimuli, for predicting who does or does not have pain from shingles or diabetes. We will also evaluate the usefulness of a new technique, counting the density of pain-sensing (nociceptive) nerve endings within the epiderrnal layer of small skin punch biopsies. Surprisingly, work by our group and others show that neuropathic pain patients usually have fewer nociceptive nerve endings in painful skin. When the amount of signal coming in from the periphery decreases, pain-processing neurons in the brain and spinal cord become hyperactive. The result can be pain in the absence of tissue injury. This is similar to the development of tinnitus (ringing in the ears) when people lose hearing. Our data suggests that after shingles, PEN pain is felt by only those patients whose density of nociceptive nerve endings has been reduced below a threshold value (650 neurites/mm2 skin surface area). In Specific Aim I, we will study patients about 6 weeks after onset of shingles with quantitative sensory testing and skin biopsies, and repeat them 6 months later. We will evaluate whether data from the first set of tests, or changes between the two test sessions, can provide a marker for those who recover from pain or not. In Specific Aim II we will compare sensory testing and skin biopsy data from normal people and diabetics with and without pain to see whether there is evidence for a threshold value separating individuals with and without pain, and whether we can identify a presymptomatic state. In Specific Aim III, we plan to evaluate sensory function of the paw in rat models of pain after sciatic nerve injury. At sacrifice, biopsies will be taken from the bottom of the rat's paws as well as from the injured nerves to see whether changes in the density of nociceptive nerve endings in the foot correlate with severity of damage in the nerve and with the rat's behavior during sensory testing. The
40
Chronic Pain
goal of this research is to improve medical care for patients with chronic neuropathic pain, and facilitate research by identifying "biomarkers" that can be used as surrogate measures for the presence of neuropathic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROGENIC PATHOGENESIS OF INTERSTITIAL CYSTITIS Principal Investigator & Institution: Pezzone, Michael A.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Chronic pelvic pain is a poorly understood but sufficiently debilitating clinical condition primarily affecting women. Few diagnostic and treatment options are available for this understudied patient population, which is estimated at 9.2 million in the United States. The causes of chronic pelvic pain are numerous but may involve gynecologic, urologic, gastrointestinal, musculoskeletal, neuronal, or psychological origins as well as combinations thereof. The urinary bladder and colorecmm are two of the larger pelvic organs thought to be affected primarily in these disorders, and thus, it is not surprising that interstitial cystitis (IC) and irritable bowel syndrome (IBS) are two of the commonest causes of chronic pelvic pain. The observed overlap of chronic pelvic pain disorders such as IC and IBS suggests a common underlying etiology or even cross-organ (neurogenic) sensitization. Using a newly developed rodent model for studying afferent-mediated interactions of the pelvic organs in the rat, we will investigate the hypothesis that chronic irritation of the distal colon may adversely influence and sensitize urinary bladder afferents leading to neurogenic cystitis and its associated physiologic sequelae. The studies proposed in this application will attempt to shed more light on the overlap and etiology of chronic pelvic pain syndromes and the role of cross-organ, afferent sensitization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: VULVODYNIA
NEUROIMMUNOLOGY/CYTOKINE
ALTERATIONS
IN
Principal Investigator & Institution: Reed, Barbara D.; Family Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-AUG-2003 Summary: Hundreds of thousands of women in the United States suffer from vulvodynia a chronic burning vulvar pain of unknown cause. Millions of health care dollars are spent annually for this disorder in the United States alone, not only on management, but also on the large proportion of cases that are misdiagnosed and inadequately treated. This pain, associated with allodynia and hyperpathia, has a strong genetic predelection, with African- American women rarely being affected. The broad, long-term objectives of this proposal are to assess the differences in specific neuroimmunological characteristics between women with vulvodynia and asymptomatic controls. The specific aims include: evaluation of l) the individual cytokine/neurokine production response to stimulation of peripheral blood; 2) local changes in nerve fiber, mast cell, Substance P and serotonin density in vulvar tissue; 3) the interactions of the systemic and local immunologic systems assessed in l) and 2); and 4) the multivariable assessment of these laboratory factors with historical risk factors for vulvodynia to explore potential pathophysiologic mechanisms accounting for the historical risk factors identified. The research design involves a case-control evaluation of 100 women with vulvodynia, 100 controls matched for ethnicity, and 100 African-
Studies
41
American control women, using questionnaires, physical examinations, clinical laboratory data, cytokine/neurokine levels in stimulated peripheral blood, and neuroimmunohistological assessment of vulvar biopsy specimens for nerve fiber density, mast cells, Substance P and serotonin. Results from this study will lead to improved understanding of neuroimmunologic alterations in women with vulvodynia which will direct future therapeutic strategies for this disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROLOGICAL BASIS OF PAIN: ROLE OF CANNABINOIDS Principal Investigator & Institution: Walker, J M.; Professor and Chairman of Psychology; Psychology; Brown University Providence, Ri 02912 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-AUG-2004 Summary: (Adapted from the Investigator's Abstract) The neurobiological basis of pain and the neural circuits that underlie pain perception and pain inhibition remain fundamental problems for neuroscientists. Much research in the past 25 years has focused on mechanisms in the brain that modulate pain sensitivity, especially those mechanisms related to the neurotransmitters and neuromodulators that control acute and chronic pain. Marijuana has been used for pain relief for centuries, but only recently has the mechanism of its actions on the neural processing of painful inputs been studied. Cannabinoids depress the reaction of nociceptive neurons in the spinal cord, lateral and medial thalamus. This action takes place by effects of cannabinoids on specific brain structures, the spinal cord, and the peripheral nerve itself. Besides depressing acute or nociceptive pain, cannabinoids are active in models of chronic pain, inflamation neuropathic pain and in an electrophysiological model of windup. Virtually nothing is known about the neuronal mechanisms of cannabinoid suppression of the pathological pain produced by nerve injury, which is the subject of this renewal application. The proposed experiments examine the effects of a cannabinoid agonist on pain behavior and spinal neural processing of tactile inputs in rats with chronic constriction injury of the sciatic nerve. The proposed studies further examine the effects of a cannabinoids on abnormally high levels of spontaneous discharge, the hyper excitability of mild and noxious mechanical stimuli and responses to stimulation of different peripheral fiber types. Pharmacological specificity will be examined using selective CB1 and CB2 cannabinoid receptor antagonists. These studies may shed light on the actions of endogenous cannabinoids in chronic pain because any effects of a cannabinoid antagonist that is opposite to that of an agonist may be the result of blockade of an endogenous modulator of the cannabinoid receptor. The sites of action of the drug will be examined in studies in which the compounds are applied locally to a specific brain region (the dorsal periaquductal gray), the spinal cord, the dorsal root ganglion or at the site of injury. The results of these studies will reveal mechanisms by which cannabinoids modulate the pathological pain, and suggests future studies directed at determining the role of endocannabinoids in pain processing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: NEUROTHERAPY OF FIBROMYALGIA Principal Investigator & Institution: Nelson, David V.; Behavioral Neuroscience; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Fibromyalgia (FM) is one of the most puzzling of the chronically painful disorders. It involves a core symptom of chronic widespread
42
Chronic Pain
musculoskeletal pain at specific tender point (TP) sites on physical examination and is typically accompanied by fatigue, disordered sleep, cognitive complaints, an array of other somatic complaints, as well as psychological distress and significant impairments in functioning. Although largely championed and defined by rheumatologists, FM is now increasingly recognized to have a basis in central nervous system dysfunction. Treatments to date have been only partially effective and typically of modest benefit. Many persons with FM remain persistently dysfunctional and often disabled. This has given greater impetus for patients to seek complementary and alternative medicine (CAM) therapies. Within the scope of CAM, recent developments in biofeedback using electroencephalograph (EEG) or brainwave information have suggested some potential for application to FM. A novel variant of EEG biofeedback known as the Flexyx Neurotherapy System (FNS) uses very small pulses of electromagnetic energy to stimulate changes in brainwave patterns. The specific aim of this study is to evaluate the efficacy of FNS for the reduction of FM symptoms in a randomized, double-blind, placebo-controlled trial comparing two groups each of 20 patients who receive either the active intervention or a sham treatment for the same number of sessions. It is expected that immediately at the conclusion of treatment and at 3- and 6-month follow-up, patients receiving the active treatment will score significantly better on the primary outcome measure, the Fibromyalgia Impact Questionnaire total score. In terms of secondary outcome measures, it is further expected that patients receiving the active treatment will demonstrate significantly decreased heat sensitization (an objective indicator of abnormal central nervous system activity), fewer TPs and higher pressure thresholds to elicit TPs, less fatigue, improved cognitive functioning, reduced psychological distress, less depression, and improved quality of sleep. Preliminary data from this exploratory/developmental project will justify larger randomized, doubleblind, placebo-controlled clinical trials of FNS and comparisons to other treatments for FM, and may provide a basis for investigating correlates and potential mechanisms of change. This program of research may contribute to immediate clinical applications to reduce FM symptoms and to better understanding of mechanisms of FM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROTROPHIC MECHANISMS IN LUT PLASTICITY WITH CYSTITIS Principal Investigator & Institution: Vizzard, Margaret A.; Associate Professor; Neurology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Interstitial cystitis (IC) is a chronic inflammatory bladder disease syndrome characterized by urinary frequency, urgency, suprapubic and pelvic pain. Although the etiology and pathogenesis of IC are unknown, numerous theories including; infection, autoimmune disorder, toxic urinary agents, deficiency in bladder wall lining and neurogenic causes have been proposed. Pituitary adenylate cyclase activating polypeptide (PACAP) exerts diverse and prevalent roles in the lower urinary tract (LUT). Sensory fibers expressing PACAP have been identified in the bladder wall and in suburothelial plexuses, PACAP expression in the micturition reflex pathway is upregulated following chronic cystitis and pharmacological agents that block PACAP receptor function reduce bladder overactivity after cystitis. PACAP expression can be regulated by neurotrophins; conversely, recent studies have also suggested that PACAP may regulate neurotrophin receptor tyrosine kinase expression and activation. Cystitis markedly alters the profile of neurotrophin expression in
Studies
43
bladder tissues. Thus, the resulting changes in target organ growth factor levels may drive the neurochemical and functional plasticity in the micturition pathway with cystitis. The overall hypothesis for our work is that pain and micturition dysfunction in IC involves an alteration in bladder smooth muscle, urothelium and sensory physiology. The central hypothesis is that the VIPIPACAP system is a prominent modulator of bladder sensation and function and the inflammation-induced changes in neurotrophic factors and/or neural activity arising in the bladder alter PACAP/PACAP receptor expression in LUT to mediate altered micturition function in IC. The following three aims test these hypotheses. 1). To characterize PACAP and PACAP receptor expression in urothelium, bladder smooth muscle and bladder afferent cells in the lumbosacral DRG; 2). To establish the functional relationships between PACAP and neurotrophin systems in the normal micturition reflex pathway and after cystitis.; 3). To evaluate the physiological roles of PACAP and neurotrophins in the micturition reflex pathway using PACAP knockout mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL CELL LINES ALLEVIATE CHRONIC NEUROPATHIC PAIN Principal Investigator & Institution: Eaton, Mary June.; Neurological Surgery; University of Miami Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 31-MAR-2002 Summary: Painful sensations are a frequent and often chronic sequela of paraplegia and quadriplegia following partial or complete lesions of the spinal cord. Current research of mechanisms of chronic pain in these patients has suggested a related loss of inhibitory neurotransmitters and growth factors in the injured cord that may be responsible, at least in part for the onset of this condition. Efforts to restore neurotransmitter levels by pharmacological intervention has proven effective for short periods, but they are difficult to monitor and manage. We hypothesize that: 1. By exogenously modifying within the spinal cord, the levels of neurotransmitters such as serotonin (5HT), gammaaminobutyric acid (GABA), acetylcholine (ACh), and neurotrophic factors such as brainderived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), the sequela of altered sensory perceptions associated with chronic pain after peripheral injury will be partially ameliorated and the intrinsic inhibitory neurotransmitter systems enhanced. We will test this hypothesis by transfecting the cDNA sequences encoding the synthetic enzymes and neurotrophic factors associated with restoration of the endogenous inhibitory neurotransmitter system into two immortalized raphe precursor cell lines and clones which secrete biologically active neurotrophic factors and neurotransmitters will be isolated. These novel cell lines will be transplanted int the injured spinal cord and tested for their ability to ameliorate chronic painful hypersensitivity after peripheral nerve injury. We further hypothesize that: 2. The altered biochemical environment of the spinal cord after peripheral nerve injury leads to reversible changes in the pain centers of the dorsal horn of the spinal cord. This altered biochemistry may inhibit or facilitate the long-term recovery of normal sensory responses depending on the relative secretion and release of neurotrophic factor and neurotransmitter signalling substances. We propose to immunohistochemically and biochemically define the levels of inhibitory neurotransmitter after induced peripheral nerve injury. We will further determine by in situ hybridization the altered expression of the synthetic enzymes for the inhibitory neurotransmitters after injury. We will also use behavioral measures of responses to normally non- painful and painful stimuli to relate the changes in spinal cord inhibitory biochemistry to the hypersensitivity to normally non-painful stimuli.
44
Chronic Pain
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ONLINE PAIN MANAGEMENT EDUCATION FOR PHYSICIANS Principal Investigator & Institution: Harris, John M.; President; Medical Directions, Inc. 6101 E Grant Rd Tucson, Az 85712 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2003 Summary: (provided by applicant): The long-term objective of this project is to develop a cost-effective Internet-based education program that will improve the performance of physicians and other health professionals in managing patients with chronic pain. While pain is associated with a number of disease states, chronic pain may have behavioral and social effects that extend beyond the direct health effects of the associated disease. In such cases the underlying disease, e.g. an advanced malignancy, may not be amenable to cure, but the painful consequences may be treatable. Unfortunately, there is considerable evidence that health care professionals consistently undertreat chronic pain. The primary reason for this is thought to be inadequate professional education. We intend to develop an online, problem based, educational program in pain management that will improve physician and other health professional knowledge, attitudes, beliefs, and skills in managing chronic pain. This program will be based on well-documented concepts of adult learning theory and expand on a successful Internet-based educational model. The eventual commercial product will be a multihour continuing medical education program that will be sold to physicians and other health professionals via a commercial Internet site and to medical organizations via a robust Internet-based delivery platform. We will also develop a reliable and clinically valid survey tool that can be used to assess the effectiveness of this and other professional education programs in pain management. The research aims of the Phase I study are to refine the learning objectives of the online educational program, develop and validate a survey-based chronic pain education assessment tool based on these objectives, develop a written curriculum on pain management, and subject this curriculum to outside expert review. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: OPIOID ADDICTION IN PRIMARY CARE CHRONIC PAIN PATIENTS Principal Investigator & Institution: Fleming, Michael F.; Professor; Family Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): Background: Non-malignant chronic pain is an increasingly common and complex clinical problem. Primary care physicians are being encouraged by patients, pain specialists, and policy makers to increase the use of chronic opiold therapy as a primary treatment for chronic pain. Some of the major concerns of both physicians and leaders of health care systems are the development of addiction, drug-seeking behavior, and diversion in patients receiving chronic opioid therapy. Specific aims: The proposed study is designed to estimate the current and lifetime prevalence of drug use and dependence in patients receiving chronic narcotics from their primary care physicians. Drugs of interest include licit opioids, illicit opiolds, sedatives, cocaine, stimulants, cannabis, and alcohol. Secondary questions of interest involve levels of pain control on narcotics, co-morbidity issues, health status, and quality of life issues. Methods: A prevalence study will be conducted in six health care systems in Dane and Milwaukee counties in Wisconsin. A sample of 1,000 patients will
Studies
45
be recruited from the practices of approximately 200 primary care physicians who work in the six health care systems. Inclusion criteria include taking prescription opioids for at least the past 30 days, age between 18 and 70, a diagnosis of chronic non-malignant pain, and narcotics prescribed by a primary care clinician. Face-to-face interviews will be conducted utilizing the SDSS and PRISM to assess current and lifetime drug addiction. Patients will also complete questionnaires to assess the secondary questions of interest. The physicians will participate in a short interview to assess their current approach to the use of narcotics for chronic pain. Summary: This would be the first large prevalence survey conducted in the US health care system to assess rates of addiction in a primary care chronic pain population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPIOID CELL TRANSPLANTS FOR PAIN ALLEVIATION Principal Investigator & Institution: Sagen, Jacqueline; Professor; Neurological Surgery; University of Miami Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2001; Project Start 10-APR-1997; Project End 31-JAN-2004 Summary: (Applicant's Abstract) The transplantation of cells or tissue into the CNS is a potential means of achieving sustained delivery of naturally derived pharmacologically active substances for the alleviation of chronic disorders. Work in our laboratory has demonstrated that adrenal medullary or chromaffin cell transplants in the spinal subarachnoid space can alleviate pain symptoms in several animal models. This most likely involves the release of pain-reducing neuroactive substances, such as opioid peptides and catecholamines, from the transplanted cells. A significant advantage of the transplant approach for the chronic pain patient is the potential ability to provide a continually renewable source of analgesic agents, reducing or eliminating the need for repeated narcotic administration. As a result of promising findings in animal studies, clinical studies have been initiated at several centers in patients with cancer pain, with encouraging results. The goals of the proposed studies are to understand the mechanisms, long-term consequences, and potential limitations of these transplants in the CNS. Pharmacologic and biochemical analyses will be done in order to determine transplant interactions with host spinal receptors, the contribution of opioid and other neuropeptides to pain reduction, and tolerance and cross-tolerance to traditional pharmacotherapies. The mechanisms of the transplants in reducing both acute and chronic pain processes may be distinct, and will be evaluated using selective nociceptor activation and acute and chronic pain models. It is thought that chronic pain such as that consequent to peripheral nerve injury or inflammation results from a cascade of neuropathological events leading to persistent hyperexcitability, including activation of NMDA receptors and the production of nitric oxide and cyclic GMP. Clinically, in spite of advances in pain management, some of the most debilitating disorders are those associated with peripheral or central nerve lesions and chronic inflammation, and are poorly or inadequately controlled by traditional pharmacotherapies. Recent studies in our laboratory have suggested that adrenal medullary or chromaffin cell transplants can alleviate symptoms of chronic pain due to peripheral nerve injury and inflammation, and may do so via intervening in the NMDA/NO cascade. Thus, if successful, the findings from these studies could lead to a novel approach in the long term therapeutic intervention for alleviation of chronic pain syndromes, particularly those refractory to traditional pharmacotherapies, who would benefit greatly by improved quality of life free from pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
46
Chronic Pain
•
Project Title: OPIOID RECEPTOR GENE TRANSFER-PAIN AND TOLERANCE Principal Investigator & Institution: Huang, Li-Yen M.; Professor; Marine Biomedical Institute; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 25-AUG-2001; Project End 31-JUL-2006 Summary: The long-term goal of this research is to develop gene therapy for chronic pain. Opiates have remained to be the drugs of choice for treating patients with severe pain. The side effects of opiates, including respiratory depression, tolerance and dependence, have often limited their use. The focus of this grant is to design viral vectors that allow for efficient and stable delivery of wild type or mutant mu opioid receptor (muOR) genes to sensory neurons. We hypothesize that appropriate muOR gene delivery and expression in dorsal root ganglion (DRG) neurons will lower the doses of mu-opioids required for analgesia and reduce tolerance, thus decreasing the side effects of opioids. To test this hypothesis, we will (1) deliver the wild type or mutant mu OR gene into sensory neurons using an adeno- associated virus (AAV) vector, (2) evaluate the effects of mu- opioids on pain behaviors in inflamed rats injected with recombinant AAV-mediated muOR transgene (rAAV-muOR), (3) evaluate the effects of mu-opioid in tolerant rats that receive injections of rAAV-muOR and (4) evaluate the effects of mu-opioids on membrane conductance and receptor trafficking in rAAV-muOR- transduced DRG neurons isolated from non tolerant and tolerant rats. The experiments will be performed on rats treated with complete Freund's adjuvant (CFA) and on DRG neurons isolated from those rats. Pain behaviors will be monitored by paw withdrawal latencies, membrane currents will be measured with perforated patch electrodes and receptor trafficking will be examined with immunofluorescence staining and receptor binding assays. These experiments will establish the feasibility of a genetic approach to pain treatment. If successful, the study will provide clinicians with a new tool to treat patients with severe pain and provide researchers a model for studying the role of opioid receptor regulation in the development of opioid tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: OPIOIDS WITH DELTA ANTAGONIST AND MU AGONIST ACTIVITY Principal Investigator & Institution: Coop, Andrew; Assistant Professor; Pharmaceutical Sciences; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: Chronic clinical pain remains poorly treated. The use of mu opioid analgesics such as morphine can treat the pain, but the severe undesired effects of morphine and other mu agonists limit their use. Indeed, the rapid development of tolerance causes ever-increasing doses to be administered, increasing the severity of the undesired effects. Recent work has shown the coadministration of a delta opioid antagonist, together with morphine causes a slower build-up of tolerance than administration of morphine alone. Further, the use of a peptide with a dual profile of mu agonism/delta antagonism has been reported to give rise to little tolerance. Thus, the aim of the current research is to develop potent non-peptide mu agonists, which also possess a profile of delta antagonism. The orvinols (e.g. etorphine) are a class of potent mu opioid agonists that also interact with kappa and delta receptors, generally displaying delta agonism. Our hypothesis is that the delta efficacy of the orvinols can be reduced by the introduction of an aromatic group in a position that corresponds to the position of the indole in the indolomorphinans (e.g. naltrindole, oxymorphindole) or the benzylidene in
Studies
47
the opioid benzylidenes (e.g. benzylidenenaltrexone (BNTX)), two important classes of low efficacy delta opioid ligands. By reducing delta efficacy, decreasing kappa affinity, and retaining high mu efficacy, analogs of the orvinols with the desired profile will result. The approach to be used consists of the development of a pharmacophore model of delta antagonism using a novel molecular modeling approach, and the selection of target molecules with a suitably positioned aromatic ring. The novel model will be tested through the synthesis of simple morphinans containing aromatics that satisfy the pharmacophore. Information garnered from the simple morphinans will be applied to the design and synthesis of the target 5,14-bridged morphinan based orvinols selected by the model. Novel chemical methodology will be developed and applied to the synthesis of the 6,14-bridged targets, analogs very closely related to the orvinols. The ultimate goal of this proposal is to develop potent mu opioid analgesics, to which tolerance develops slowly, or not at all, in order to reduce the undesired effects seen in the chronic treatment of clinical pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL L GLUTAMINE THERAPY FOR SICKLE CELL ANEMIA Principal Investigator & Institution: Niihara, Yutaka; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2001; Project Start 10-APR-1998; Project End 31-MAR-2002 Summary: Sickle cell anemia is one of the most common and devastating hereditary disorders with significant morbidity and mortality affecting individuals of African American heritage. No safe, effective therapy is yet available. Within the last few years, hydroxyurea has been used in an increasing number of sickle cell anemia patients. However, hydroxyurea is a chemotherapeutic agent with myelosuppressive effects and its long term safety is still unknown. An ideal agent would be one that is readily available, effective and safe even with chronic use. Based on previous data from this laboratory on sickle red blood cell metabolism, we have conducted a pilot study recently using L-glutamine as an oral agent. The four week open label study involving seven homozygous hemoglobin S patients showed promising results by demonstrating improvement in redox potential and decrease in chronic pain in all patients. In addition a subsequent 12 week study involving 4 patients showed significant decrease in the frequency of painful sickle crises. On the basis of these data we propose to expand the study of L-glutamine therapy for sickle cell anemia to a double blind study to observe objectively the effect of the amino acid in sickle cell anemia patients in terms of their clinical status and hematological parameters. Our long term goal is to establish the usefulness and safety of L-glutamine in therapy of sickle cell anemia. Our specific aims in this project are to determine the effect of oral L-glutamine on 1) sickle red blood cells at cellular and biochemical level, 2) clinical status of the sickle cell anemia patients including the incidence of painful crisis, narcotic requirement for acute or chronic pain, 3) sickle cell anemia patients' hematological parameters including hemoglobin, hematocrit, reticulocyte count,and hexokinase level, and 4) adverse effects attributable to L-glutamine. L-glutamine is an amino acid that has been used widely for other purposes and shown to be safe by others. It is also inexpensive and readily available. The pilot data are promising. This project will provide the pathophysiologic basis for the use of L-glutamine and will evaluate the efficacy of L-glutamine in the therapy of sickle cell anemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
48
Chronic Pain
•
Project Title: ORWH: SCOR ON SEX AND GENDER FACTORS AFFECTING WOMEN'S * Principal Investigator & Institution: Greenspan, Joel D.; Associate Professor; Basic Dental Sciences; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This multidisciplinary SCOR is devoted to the study of the mechanisms of chronic or persistent pain with specialized focus on 1) sex-related factors that influence pain, and 2) painful clinical conditions that demonstrate a high prevalence in women. The Center's research program is diverse, and ranges from molecular studies to systems physiology studies to clinical studies. Our working model is that research on pain has clearly shown that a person's sex is an important factor in determining their perception of, and response to, painful stimulation and pathological pain. Several physiological and psychological mechanisms have been proposed to account for these sex differences, yet many hypotheses remain to be adequately tested. This SCOR would direct its efforts to evaluating physiological models of sex-related pain differences, including the influence of gonadal hormones. Additionally, this Center would evaluate pathophysiological models of chronic pain conditions that are more prevalent in women, focusing on temporomandibular joint disorders (TMD) and the visceral pain associated with conditions such as irritable bowel syndrome (113S). This Center would facilitate the transfer of basic scientific knowledge to the study of persistent pain in humans, and ultimately to the development of new methods of diagnosing and treating these conditions in the general population. One clinical and two basic science projects constitute the scientific basis of the application. The two principal objectives of this SCOR are: 1) To elucidate the underlying mechanisms associated with sex differences in persistent pain of deep muscle and visceral origin. Human and animal studies will explore hypothesized physiological mechanisms of sex differences in pain, including opioid receptor expression, peripheral nociceptor sensitivity, CNS sensitization, and CNS ascending/descending modulation, as well as the influence of gonadal steroids on these mechanisms. All three projects address this objective. 2) To explore the neural basis of temporomandibular disorder (TMD) pain, with special emphasis upon sex-related hypotheses. TMD is the major persistent orofacial pain condition of deep tissue origin. It shows a large prevalence in women of childbearing age. The pathophysiology of TMD is poorly understood, but several hypotheses based on sex-related factors have been proposed. Two of the proposed projects (#1and #3) direct efforts explicitly to evaluate such hypotheses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PAIN AND BEHAVIORAL SYMPTOMS IN DEMENTIA: A PILOT STUDY Principal Investigator & Institution: Miller, Lois L.; Population Base Nursing; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-JAN-2005 Summary: The purpose of this study is to test an intervention focused on the treatment of chronic pain for institutionalized older adults with dementia, with the intention of also reducing protective behavioral symptoms, such as aggression. A secondary purpose is to understand the mechanism that underlies the relationships among morning care, observed pain, and protective behavioral symptoms, both in the absence and presence of the proposed intervention. Older persons are at special risk for unidentified and under treated pain, often receiving significantly less analgesic
Studies
49
medications than their cognitively intact peers. In addition, protective behavioral symptoms are exhibited by as many as 90 percent of persons with dementia. Although researchers and clinicians have hypothesized an association between pain and protective behavioral symptoms, little research has explored this relationship. This quasi-experimental study will use a 3-group repeated measures design with an untreated control group, to evaluate the effects of an individualized pain treatment intervention on nursing home residents with dementia. A purposive sample of 30 residents who are moderately to severely cognitively impaired, have at least one potentially painful chronic musculoskeletal condition, and exhibit protective behavioral symptoms (resistiveness to care, verbal and/or physical aggression) will be selected from 3 nursing homes (n=10 per facility). The Comfort And Responsiveness Enhancement (CARE) intervention, implemented by an advanced practice nurse consists of two components: 1) an analgesic drug component and 2) a psychosocial component. The two treatment components will be introduced in opposite sequence in intervention facilities, and during the final phase each participant will be exposed to the additive CARE intervention, which is expected to be associated with the best outcomes for participants. Outcomes of interest include self- report of pain, observed pain, protective behavioral symptoms, analgesic drug use, and psychosocial intervention use. Analysis of the effects of the intervention will use ANOVA if possible, or the corresponding nonparametric analytic technique (Wilcoxon signed rank sum tests). Content analysis of field notes kept throughout the intervention will be used to modify the intervention and evaluate the feasibility of testing it in a larger randomized clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PAIN REGULATORY SYSTEM DYSFUNCTION IN CHRONIC PAIN Principal Investigator & Institution: Bruehl, Stephen; Anesthesiology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 15-JAN-1999; Project End 31-DEC-2002 Summary: Elevated resting blood pressure (BP) is consistently related to diminished acute pain sensitivity. Ibis cardIovascular-related antinociception (mediated in part by endogenous opioids) is an important component of adaptation to pain in healthy individuals. it is unknown whether these antinociceptive mechanisms operate normally in chronic pain patients. Previous research indicates deficits in endogenous opioid levels in chronic pain patients, although little is known about the functional impact (e.g., diminished analgesia) of these deficits. Given the mediating role of endogenous opioids in cardiovascular-related antinociception and likely opioid deficits in chronic pain conditions, it is hypothesized that chronic pain patients will display alterations in these normally adaptive cardiovascular-pain regulatory relationships. The long-term objective of these studies is to explore the nature of dysfunction in the endogenous pain regulatory systems of chronic pain patients. improved understanding of the mechanisms contributing to chronic pain has the potential to lead to improved treatment for chronic pain patients. The specific aims of these studies are threefold: 1) examine the relationship between resting blood pressure and acute pain sensitivity in both neuropathic and nociceptive chronic pain patients as contrasted to normals, 2) examine possible differences in degree of endogenous opioid mediation of the relationship between resting blood pressure and acute pain sensitivity across the pain patient and normal control subgroups, and 3) examine whether endogenous opioid dysfunction in chronic pain is progressive and therefore related to pain duration. Sixty chronic pain patients (study l=neuropathic back pain, study 2=nociceptive back pain)
50
Chronic Pain
and 60 healthy controls will undergo a laboratory ischemic pain stimulus once under placebo and once under opioid blockade with naloxone (randomized, counterbalanced order). in both sessions, resting BP will be determined at baseline. Pain patients will also rate their clinical pain before and after drug administration. it is expected that controls will display significant negative correlations between resting BP and acute pain sensitivity, which is at least partially eliminated by naloxone. Pain patients are expected to demonstrate no correlation or a positive correlation between resting BP and acute pain responsiveness, and will be unresponsive to opioid blockade. Greater pain duration is expected to be associated with smaller changes in the BP/pain relationship in response to opioid blockade. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PAIN SIMILARITIES IN BREAST CANCER AND FIBROMYALGIA Principal Investigator & Institution: Burckhardt, Carol S.; Professor; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-AUG-2004 Summary: (from applicant's Abstract) The majority of women with breast cancer are likely to survive for many years after the initial diagnosis and treatment. Unfortunately, long-term disease and treatment-related symptoms, such as chronic pain, can have wide-ranging consequences for health, functioning, and life quality. The purpose of this pilot project is to describe the characteristics of the chronic pain experienced by women with breast cancer who are post-breast cancer surgery with particular emphasis on the description of widespread pain, The specific aims are to: (1) describe characteristics of the chronic pain experienced by women who are post-breast cancer surgery; and (2) compare and contrast the pain characteristics, sensory thresholds, upper body muscle strength and impairment, syndrome impact, health status, and quality of life of women with neuropathic pain only with that of women who meet criteria for fibromyalgia, a specific syndrome of widespread pain. The immediate goal of this pilot project is to test an assessment strategy for characterizing the pain, impairment, and impact. The long term goals are to use the information to support the development of better diagnostic assessments of post-breast cancer surgery pain and the development of innovative early intervention strategies to prevent widespread pain and increase the functioning, health and quality of life of women who have post-breast cancer surgery pain. The study will use a descriptive design in which 30 women, with either post-surgery chronic pain that is limited to the operated side or widespread body pain, will be assessed for descriptions of the pain, muscle strength of the upper extremities, lymphedema, tender points, joint tenderness and swelling, sensory integrity, thermal sensation, health status, and quality of life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: FACTORS
PAIN,
SUPRASPINAL
SEROTONIN
AND
NEUROTROPHIC
Principal Investigator & Institution: Hackshaw, Kevin V.; Assistant Professor; Internal Medicine; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Fibromyalgia comprises a subset of hyperalgesic or allodynic syndromes characterized by a dysregulation of nociceptive processing and neuroendocrine function. Chronic generalized pain together with decreased endocrine and autonomic responsiveness to stress has been observed. Clearly, supraspinal systems regulate
Studies
51
nociceptive pathways, but our understanding of the neuromodulators participating in chronic pain pathways is quit incomplete. Therapeutically, drugs that alter serotonergic neurotransmission show modest effectiveness in these disorders. This study will utilize in vivo microdialysis to investigate monoamine release in supraspinal sites important in endocrine (paraventricular nucleus of the hypothalamus) and pain regulating (ventral lateral thalamus) systems in an animal model of chronic pain. In addition, the effects of chronic pain on responsiveness of the autonomic nervous system will also be assessed. Neurotrophic factors NGF, FGF-1 and FGF-2 are prominently expressed in the central nervous system however, there is a paucity of information on how their expression changes in the setting of chronic pain. In situ hybridization and immunohistochemical localization of these growth factors will be conducted on brain from Sprague-Dawley rats with adjuvant induced arthritis (a model of chronic pain), rats having undergone partial sciatic nerve ligation (a model of acute pain) and sham treated control rats. In vivo experiments will utilize antigens oligonucleotide technology to modulate c-fos, NGF, FGF-1 and FGF-2 expression. Microdialysis will allow us to dynamically assess Serotonin, Substance P and NGF levels in selected regions of rat brain following antigens oligonucleotide delivery. This proposal will provide a novel approach to dynamically measure critical compounds involved in nociceptive transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGIC PLASTICITY IN THE PRESENCE OF PAIN Principal Investigator & Institution: Eisenach, James C.; Professor; Anesthesiology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: There have been rapid advances in our understanding of neurophysiologic changes that underlie the generation and maintenance of hypersensitivity states in animals, and these are presumed to underlie the phenomena of spontaneous pain, hyperalgesia, and allodynia in patients with pain. The distinction between 'acute' and 'chronic' pain is becoming blurred, as one can demonstrate many of these 'chronic' phenomena in animal models of brief injury (e.g., paw incision, intradermal capsaicin injection). Despite these advances, clinical application or even testing of these concepts has lagged far behind. This Center's goal is to prove mechanisms that underlie altered analgesic drug responses following generation of hypersensitivity states in the laboratory and to test the resultant hypotheses and their clinical relevance in humans. Five Projects are proposed, examining (I) mechanisms behind the shift in spinal circuitry activated by alpha2-adrenergic agonists and reduction in opioid agonist efficacy following peripheral nerve injury, (II) regional spinal opioid ligand efficacy using a functional G-protein activation assay and changes in efficacy in hypersensitivity and chronic drug exposure, (III) hormonal influences which determine the large sex difference observed in analgesic response to cholinergic agents, (IV) patterns of selfadministration of opioids in animals with and without hypersensitivity following peripheral nerve injury, and (V) human relevance of hypotheses generated by (I-IV). Laboratory efforts are linked in complex, overlapping fashion, and are supported by an Animal and General Research Services Core, which includes a much needed model development section, and an Administrative Core, which will encourage discussion, sharing, and focus. Perhaps most important to this Center is application of unique pharmacologic tools at this institution and expertise in trial design to assemble, through Project V, 4 key clinical studies to test important translational and methodological hypotheses, including systemic opioid efficacy in chronic pain, role of hypersensitivity in postoperative and chronic pain, and predictive value of pharmacologic testing in
52
Chronic Pain
volunteers to pain in patients. Thus, this Center fills an important void in bringing togther clinicians and laboratory scientists to explore novel therapeutics and mechanisms of pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGY FOR CHRONIC PAIN: AN INTERACTIVE CD ROM Principal Investigator & Institution: Triant, Randi S.; New England Research Institutes, Inc. 9 Galen St Watertown, Ma 02472 Timing: Fiscal Year 2001; Project Start 25-SEP-1998; Project End 31-MAR-2003 Summary: (adapted from applicant's abstract): Pain, the most common symptom of disease or disability, is an important but neglected worldwide public health problem. Chronic, nonmalignant pain affects an estimated 34 million Americans, and its effects on personal and job-related productivity and quality of life are immense. Although pain is one of the most common reasons people seek medical attention, treatment is frequently inadequate. Physicians have an ethical obligation to manage pain and relieve the patient's suffering, but the assessment and management of pain occupies little time in medical school curricula or in postgraduate education for physicians and medical students. Barriers to proper treatment include inadequate pain assessment, poor provider-patient communication, and lack of knowledge on appropriate use of analgesics. The purpose of this Phase II SBIR is to produce a comprehensive, CMEaccredited, interactive CD-ROM educational program that will enhance the skills of primary care physicians and other health professionals in the diagnosis and pharmacological management of patients with chronic pain. Specific aims are: 1) establish the scientific content to focus on treatment with opioid and non-opioid medications, 2) produce a marketable, comprehensive educational CD-ROM program, and 3) establish the effectiveness of the program on the diagnosis and management of patients with chronic pain. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PHYSIOLOGY OF ATP RELEASE IN CHRONIC PAIN Principal Investigator & Institution: Matsuka, Yoshizo; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant) Chronic inflammatory and neuropathic pain is a problem of considerable clinical relevance. Understanding the mechanisms underlying development and maintenance of chronic pain would be a major step towards rational treatment of such pain conditions. Considerable evidence links chronic pain of neuropathic origin with increased excitability and abnormal signal generation in primary afferent neurons within sensory ganglia. Chemically-mediated cross-excitation between neurons in sensory ganglia has been proposed as one major mechanism by which abnormal discharges can be generated in pathological pain states. However, the identity of the chemical mediator of cross-excitation is unknown. Adenosine triphosphate (ATP) is released within sensory ganglia following neuronal activation and was shown to activate receptors on somata of sensory neurons. The overall goal of this proposal is to directly test the hypothesis that ATP is the chemical mediator of crossexcitation and to determine how release of ATP changes in pathological pain states. The specific aims are to: 1) determine the involvement of released ATP in cross-excitation of
Studies
53
neurons within sensory ganglia, 2) determine the changes in basal and stimulus-evoked ATP release after peripheral inflammation, 3) determine the changes in basal and evoked ATP release after induction of sciatic neuropathy, 4) compare ATP release from different types of isolated and labeled DRG neurons. Cross-depolarization evoked by peripheral nerve stimulation will be measured during intracellular recordings from neurons in dorsal root ganglia (DRG). ATP receptors on sensory neurons will be manipulated by application of selective agonists and antagonists to influence evoked cross-depolarization. ATP release will be measured by the luciferin-luciferase assay in DRG perfusates. ATP release from acutely isolated DRG neurons will be measured using detector patches. These studies will be carried out first under normal conditions and then compared to results obtained after induction of a) peripheral inflammation, and b) peripheral neuropathy in rats. The acquired knowledge may lead to the development of novel therapeutics targeting abnormal excitability changes in sensory neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREEMPTIVE ANALGESIA IN RECOVERY FROM HYSTERECTOMY Principal Investigator & Institution: Ochroch, Edward A.; Anesthesia; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 11-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Over half of the over 23 million surgical procedures are accompanied by inadequately treated pain. Pain interferes with bodily functions such as breathing, blood pressure regulation, digestion etc. It inhibits the patient s ability to participate in postoperative care regimens, and clearly increases the risk of postoperative respiratory complications. After discharge, the poorly controlled pain continues to plague patients. The pain associated with surgery can lead to chronic pain syndromes due to sensitization of the central nervous system (CNS). We have chosen to use trans-abdominal hysterectomy (TAH) as a model operation because 600,000 women a year have hysterectomies, and women are more prone to suffering chronic painful syndromes. Preemptive analgesia is an intervention designed to decrease pain and improve patient recovery from surgery by initiating an analgesic regimen prior to the onset of the painful stimuli. There is clear animal based research and a growing body of human clinical research that preemptive analgesia can reduce pain and analgesic needs following surgery. Recent work has extended the proof of benefits in the form of decreased pain and increased activity to well after discharge from the hospital. This research application proposes to examine the short- and long-term benefits of aggressive preemptive epidural analgesia in patients undergoing TAR Pain during hospitalization and after discharge, activity levels, and return to preoperative function will be quantitatively assessed with validated outcome measures. Dr. Ochroch, an Assistant Professor of Anesthesiology at the University of Pennsylvania, is applying for a Clinical Investigator Award (K23) to pursue an academic career focusing on improving recovery from surgery. He has a serious interest in this area as evidenced by his involvement in current and proposed research. This application requests support to allow him to undertake a comprehensive career development program including: 1) a Masters in Biostatistics and Epidemiology under the mentorship of Dr. Brian Strom, 2) a research preceptor ship with Drs. John Farrar and Allan Gottschalk and Mark Morgan, and 3) the proposed research project. These activities will provide him with the skills and experience to pursue a successful career of meaningful funded research as an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
54
Chronic Pain
•
Project Title: PULMONARY COMPLICATIONS IN PEDIATRIC SICKLE CELL DISEASE Principal Investigator & Institution: Smith-Whitley, Kim; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2003 Summary: (Adapted from the applicant's abstract) This study is designed to: 1) identify risk factors of severe acute chest syndrome (ACS) and chronic pain in children with sickle cell disease (SCD), 2) develop a clinical score for ACS based on clinical severity, 3) evaluate the role of endothelin-1 and phospholipase A2, biologic markers of inflammation and vascular tone, and 4) develop a clinical staging system for chronic pulmonary changes in children with SCD. Kim Smith-Whitley, M.D., Assistant Professor of Pediatrics at the University of Pennsylvania School of Medicine and an attending physician in the Department of Hematology at the Children's Hospital of Philadelphia (CHOP), will design and conduct this study over five years. This project is an ideal vehicle for Dr. Smith-Whitley to develop the skills she will need to become an independent clinical researcher. She will work under the direction of Kwaku OheneFrempong, M.D., an international expert in SCD and Director of the Comprehensive Sickle Cell Center at CHOP. In this academic institution, Dr. Ohene-Frempong will provide direction in clinical research study design and management as well as expertise in academic medicine career development, clinical teaching skills, and program administration. He will also contribute his expertise in the clinical care of children with SCD at an institution that provides health care services for over 500 children with SCD. Through this interaction, Dr. Smith-Whitley will be able to learn invaluable skills in clinical project design and performance from conception to completion and publication and develop educational and administrative skills that will allow her to pursue a career in academic medicine as a pediatric hematologist and an independent clinical researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PURINERGIC CONTROL OF MEDULLARY PAIN MODULATION Principal Investigator & Institution: Selden, Nathan R.; Neurological Surgery; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Chronic pain is a ubiquitous, debilitating and costly affliction of both children and adults. Important aspects of pain-related behavior are mediated by supraspinal mechanisms. The rostral ventromedial medulla (RVM) has both anti- and pro-nociceptive modulatory capabilities, each referable to a distinct, physiologically identified cell class. "Off-cells" are proposed to inhibit, and "on-cells" to facilitate, nociceptive processing. The remaining RVM neurons, "neutral cells", do not alter their activity in relationship to nocifensive behavior, and their role in pain modulation is currently unclear. The proposed research will employ complementary electrophysiological and anatomical approaches (single cell recording and iontophoresis, juxtacellular labeling, and immunohistochemistry) to characterize the distribution of purinergic receptors on the three cell classes. With this information, I will directly and selectively manipulate the activity of each class in order to demonstrate a specific role in nociceptive modulation. My doctoral and post-doctoral research training has centered on the functional anatomy of brainstem catecholaminergic neurons and the neurochemistry of the basal forebrain and striatum. My clinical interest as an academic pediatric neurosurgeon is in functional nervous system diseases such as spasticity,
Studies
55
medically refractory epilepsy and movement disorders. My goal is to develop scientific and clinical expertise in central nervous system electro physiology, enabling me to launch an independent and competitively funded laboratory and also to develop a clinical program of neuromodulatory treatment (deep brain stimulation) for movement disorders in children. Oregon Health & Sciences University is an ideal location to pursue these goals. The University is recognized as centers for excellence in neuroscience research and functional neurosurgery. My mentor, Dr. Mary Heinricher, is a wellestablished and highly productive basic researcher, and my institution has committed to my developing a formal program in functional pediatric neurological surgery, which will complement my basic investigational activities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPRESSIVE STYLE, SUPPRESSION AND CHRONIC PAIN Principal Investigator & Institution: Burns, John; Psychology; Finch Univ of Hlth Sci/Chicago Med Sch North Chicago, Il 60064 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Although repressive style has been implicated in the maintenance and exacerbation of chronic pain, its true effects and how these are exerted remain obscure and largely anecdotal. This project will test a potential mechanism with a substantial empirical basis. Because repressors show high tolerance during acute pain, but report high levels of chronic pain and respond poorly to multidisciplinary pain treatment, it was hypothesized that repressor pain patients routinely suppress painrelated thoughts and emotions and thus suffer the ironic effects of such suppression (e.g., rebound). Two pain-induction studies with patients are proposed to test whether ironic effects of thought suppression represent a mechanism by which repressive style affects chronic pain. The first study examines whether repressors spontaneously show short-term pain tolerance but long-term pain sensitivity similar to that shown by high anxious patients instructed to suppress pain (i.e., analog repressors). Chronic pain patients will undergo a cold pressor, and then be followed through recovery, and another physical stimulus (massage device); half of patients will be instructed to suppress pain during cold pressor. The second study examines whether repressors reveal a bias toward pain-related information and sensitivity to acute pain when their efforts at thought suppression are undermined by competing cognitive demands. Chronic pain patients will identify pain-related and positive words imbedded in a letter grid, and undergo a cold pressor, recovery, and the massage device; half of patients will perform these tasks with a cognitive load. Repressors' tendency to suppress the distress of pain may confer beneficial immediate effects, but habitual suppression may hide an underlying paradoxical preoccupation with pain that incurs substantial long-term physiological and psychological costs. Support for the proposed model will provide empirical justification and an impetus for confronting repressive style among pain patients. Moreover, findings should provide theoretical principles on which to found new intervention strategies (e.g., "regulating" suppression by engaging in cognitive exercises). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ROLE OF CATASTROPHIZING IN ADJUSTMENT TO PAIN Principal Investigator & Institution: Ehde, Dawn M.; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 04-JUN-2002; Project End 31-MAY-2007
56
Chronic Pain
Description (provided by applicant): The broad, long-term objectives of this subproject are to reduce the pain and suffering in persons with chronic pain as a secondary condition to a disability and to further test and refine a biopsychosocial model of chronic pain as it applies to persons with disabilities. The proposed study has two specific aims: (1) to evaluate the effects of a cognitive restructuring intervention on pain in a sample of adults with disabilities in a randomized clinical trial; and (2) to study the mechanisms of the effects of cognitive restructuring by determining whether treatmentrelated changes in cognitions mediate the effects of cognitive restructuring on pain. These aims will be accomplished through a longitudinal study in which persons with chronic pain as a secondary condition to a disability (N 240) will be randomly assigned to one of two experimental conditions. In the first condition, a cognitive-restructuring intervention, subjects will be instructed in cognitive strategies designed to eliminate catastrophizing and other negative thinking about pain. The second condition will be an education control intervention in which subjects will receive education about chronic pain. Measures of pain intensity, psychological functioning, pain interference with activities, participation, and medical services utilization will be collected at several time points throughout the course of the study (pre-treatment, posttreatment, follow-up). Findings from this study will increase our understanding of the efficacy of cognitive restructuring interventions as well as the causal role of catastrophizing in adjustment to chronic pain. The study will provide an important empirical test of one hypothesis derived from a biopsychosocial model of chronic pain: that cognitions influence pain experience and adjustment to chronic pain. Ultimately, these findings may also lead to the development and refinement of treatment strategies that will reduce suffering and improve functioning in persons with chronic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF LIF AND NGF IN INFLAMMATION AND CHRONIC PAIN Principal Investigator & Institution: Hulsebosch, Claire E.; Professor; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-FEB-1974; Project End 31-JUL-2006 Summary: This project addresses the regulation of neuropeptide expression in chronic pain that appears following spinal cord injury. Such pain is often a severe affliction for the victim. A model established in our laboratories to investigate the pain that follows spinal cord injury will be utilized. In this model, pain-like behaviors that appear following hemisection of the rt spinal cord are assessed. The model reproduces the salient features of post spinal cord injury in humans. Our central hypothesis is that expression of the cytokine leukemia inhibitor factor (LIF) counteracts the development of chronic pain following spinal cord injury by increasing the expression of the neuropeptide galanin and decreasing the expression of the peptides nerve growth factor (NGF), substance and calcitonin gene related peptide. This hypothesis includes a subhypothesis that LIF acts on the synthesis of the latter peptides by reducing the biosynthesis of NGF. Existing evidence suggests that increased LIF reduces manifestations of pain in peripheral neuropathy and inflammation models by altering the production of neuropeptide inter cellular messengers. However, since this is unaddressed for the pain that develops following spinal cord injury, the biosynthesis of all of the above peptides and their effects on pain-like behaviors following spinal cord injury will be characterized. Time courses of effects of injury on peptide biosynthesis will be determined by analyzing peptides in tissue from the area of injury by ELISA or RIA assays and by immunocytochemistry. Roles of these peptides in pain expression will be tested by blocking their actions during times of increased expression or adding
Studies
57
them when their expression is decreased, together with measuring pain-like behaviors in the experimental animals. The actions of LIF or NGF will be manipulated so as to increase peptide synthesis and then the action of that peptide will be blocked to establish whether modulation of peptide biosynthesis by LIF and NGF influences painlike behaviors. Effects of LIF of inflammation and associated pain will also be characterized. Insights from this work will aid in developing treatments for pain that appears following spinal cord injury, currently a clinically intractable problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF MELATONIN IN SECONDARY INSOMNIA IN THE ELDERLY Principal Investigator & Institution: Gooneratne, Nalaka S.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: Chronic insomnia affects up to 30% of the elderly and significantly impairs quality of life and daytime functioning. It is often secondary to other medical conditions, such as pain from osteoarthritis. Recent work has suggested that melatonin, a neurohormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, the primary circadian pacemaker, is decreased in elderly insomniacs. However, treatment trials in primary insomniacs have been equivocal. This has raised many questions regarding the function of melatonin such as its role in sleep-wake regulation and whether it has nocturnal sleep-promoting effects. Interestingly, pain and nonsteroidal anti-inflammatory drugs blunt melatonin rhythms. Thus, I believe that melatonin secretion is impaired in the elderly with chronic pain and that this contributes to their insomnia. To address the hypothesis, the applicant proposes the following aims: 1) A case-control study to test the hypothesis that melatonin deficiency is a risk factor for insomnia in the elderly with osteoarthritis pain and identify a threshold level to distinguish melatonin deficient patients; 2) A randomized, doubleblind, placebo controlled trial of melatonin replacement therapy in elderly insomniacs with osteoarthritis pain to test the hypothesis that melatonin deficiency is a causal factor for their development of insomnia. Analysis will include univariable and multivariable models, and receiver operator curve analysis for Aim 1, and comparison of melatonin vs. placebo treatment arms on l objective parameters for Aim 2. This protocol may provide new insights into the neurohormonal risk factors for the development of insomnia, test the model that melatonin deficiency is a causal factor for insomnia, provide a mechanistic basis for targeted melatonin replacement therapy, and provide the training necessary to conduct rigorous, independently-funded, patient-oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SELF CARE INTERVENTION FOR TMD Principal Investigator & Institution: Truelove, Edmund L.; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JAN-1989; Project End 31-AUG-2003 Summary: The goal of this randomized clinical trial is to evaluate whether complementing usual treatment with: 1) a brief intervention that focuses on educating patients in self management of TMD and, {{2) then adding a stepped care component for patients whose TMD pain persists after a trial of usual care, will be more effective than usual treatment alone. The essential concept involved in stepped care is the introduction
58
Chronic Pain
of planned increments in health care matched to patient progress in response to regular medical treatment. Stepped care regimens matching incremental increases in treatment in patient progress using nurses, for example, have been shown to be effective in enhancing the self-management of chronic medical problems, including hypertension and diabetes.}} The rationale for the proposed study is that most conservative treatments for TMD involve some degree of self care, yet patients do not generally receive sufficient education, training and support for such self care activities. Two levels of intervention are proposed as complements to usual TMD care: 1) Education in Self Care + Usual Treatment {{(n=90)}} provides education in self care delivered in small groups of TMD patients by a registered dental hygienist (RDH) before the onset of usual clinical TMD care; 2) Education in Self-Care + {{Stepped Care}} + Usual Treatment {{n=90}} uses the same self management education intervention, further supplemented by the availability and support of an RDH Case Manager, {{assigned only to TMD cases who have progressed satisfactorily as defined by a Graded Chronic Pain chore of II or higher after two months of usual treatment}}; and 3) those receiving usual treatment alone {{(n=90)}}. Treatment outcomes among groups will be compared for changes in: 1) self reported characteristic pain, jaw function/dysfunction; 2) clinical TMD measures of vertical jaw opening, muscle and joint palpation pain scores, joint sound assessment; 3) self-report measures of health care utilization and psychosocial functioning. Subjects in each of the groups will be compared to each other at baseline, 6-, 12- and 24- month follow ups. {{The overall goals of this research are to determine if management of TMD can be enhanced by complementing usual TMD treatment delivered by dentists with less costly interventions appropriate to the status of the patient that emphasize self-care for the chronic pain condition}}. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEX HORMONES, STRESS, AND PAIN IN FIBROMYALGIA Principal Investigator & Institution: Okifuji, Akiko; Associate Professor; Anesthesiology; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 11-SEP-2000; Project End 31-JUL-2005 Summary: Many chronic pain disorders are more prevalent in women. Women also exhibit greater sensitivity to experimentally induced pain. Research has suggested that sex hormones exert multiple impacts upon human CNS, including the sympathoadrenal and serotonergic functions. The primary purpose of this proposal is to test several components of a conceptual model hypothesizing how the hormonal and stress factors are related to fibromyalgia syndrome (FMS), a chronic musculoskeletal pain disorder, predominantly seen in women. We will use both laboratory and field study approaches to evaluate the effects of sex hormones in pain sensitivity, stress reactivity, and symptom perception across a menstrual cycle in women with FMS, in comparisons to healthy pain-free females (PFF) and males (PFM). Specifically, we will test sex steroid production in FMS, estrogenic effects on the sympathoadrenal functions in response to stressors, estrogenic effects on pain sensitivity, involvement of sex hormones in perimenstrual and FMS symptoms across menstrual cycle, and sleep and stress as predictors of pain, fatigue, distressed mood in FMS. A total of 300 subjects (100 each in FMS, PFF, PFM) will undergo home urine tests, daily symptom monitoring, blood and saliva sampling, and experimentally induced stress and pain testing. The laboratory testing will be repeated on 3 separate days: once during the mid-luteal phase (high estrogen E + high progesterone P), once during the perimenstrual phase (low E + low P), and once during the late-follicular phase (high E + low P). Male subjects will be scheduled using a "yoked-cycle" to female subjects. Each subject will be randomly
Studies
59
assigned to one of the two experimental conditions ("stress-priming" vs "non-stresspriming" tasks just prior to pain testing). Blood pressure and salivary cortisol will be sampled multiple times throughout the laboratory sessions. The findings from this project are expected to promote better understanding of the role of female sex hormones in noxious sensory processing in chronic pain disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SODIUM CHANNELS AND PAIN AFTER SPINAL CORD INJURY Principal Investigator & Institution: Hains, Bryan C.; Neurobiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Many patients with spinal cord injury (SCI) report moderate to severe chronic painful dysesthesias that remain refractory to typical clinical interventions. In rodent models of SCI, dorsal horn neurons become hyperexcitable and chronic pain syndromes develop. Recently, abnormal expression of voltage-gated sodium channels has been demonstrated to contribute to hyperexcitability in injured primary sensory neurons. Thus, this project is designed to expand this analysis to secondary sensory neurons in the spinal cord, i.e. to characterize the molecular basis for hyperexcitability of spinal dorsal horn neurons after injury through alterations in expression of voltage-gated sodium channels. Hypothesis 1: Temporal and spatial alterations in gene expression of voltage-gated sodium channels occurs within the spinal cord after contusion injury. Hypothesis 2: Altered expression of a candidate sodium channel contributes to the abnormal firing properties of dorsal horn neurons and chronic central pain behaviors after contusion injury. This project proposes an investigative strategy that combines molecular, immunohistochemical, electrophysiologic, and behavioral techniques to gain important and novel insights into the changes in sodium channel transcription that follow SCI, which likely contribute to the development of chronic central pain. The long-term goals are to identify clinically useful strategies for intervention and recovery after SCI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SORTING GLYCOPROTEINS
AND
TRANSPORT
OF
SPECIFIC
NEURONAL
Principal Investigator & Institution: Ambron, Richard T.; Professor; Anatomy and Cell Biology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-APR-1985; Project End 31-MAR-2005 Summary: (from applicant's abstract) Nerve injury triggers long-term alterations that require changes in protein synthesis and which may result in the restoration of function. Often, however, regeneration fails, resulting in sensory deficits, chronic pain, and paralysis. Efforts to promote growth and minimize sensory defects would be facilitated if we knew the identity of the signals that inform the cell soma that its axon has been injured and how these signals regulated the transcriptional programs that are responsible for successful regeneration. Using the nervous system of Aplysia californica as a model the applicants found that positive injury signals activated at the site of axon injury are retrogradely transported to the cell nucleus. When axoplasm containing these signals is injected into non-injured neurons, it induces the same growth and hyperexcitability that appears when the axons of these cells are injured. A similar hyperexcitability occurs after axotomy in mammalian neurons and is thought to be responsible for chronic pain. To identify the signals responsible for these changes, they
60
Chronic Pain
analyzed the axoplasm and found it to be enriched in 2 kinases, ERK and SAPK. Most of the ERK is in the phosphorylated (active) form and the applicants hypothesize that activation occurs when an influx of calcium at the lesion site activates phosphokinase C. They will manipulate calcium levels using an ionophore to see whether PKC is affected. How ERK is retrogradely transported is not known. They will inject recombinant ERK directly into the axon to monitor its transport and will use specific antibodies and subcellular fractionation of axoplasm to see if it occurs in association with an organelle. Once ERK reaches the nucleus it phosphorylates the transcription factor C/EBP. This could increase the affinity of C/EBP for DNA, alter transcription, or regulate its entry into the nucleus. Each possibility will be assessed using recombinant wild type and mutated C/EBP. Interestingly ERK is also activated by nerve inflammation, which also induces hyperexcitability. This suggests that hyperexcitability is due to ERK acting on C/EBP. They will attempt to interfere with this process by microinjecting antibodies and oligonucleotides and by using mutated ERK and C/EBP. In contrast, retrogradely transported SAPK is constitutively active, although its activity increases after injury, and it may be involved in growth through c-Jun. The investigators have antibodies and recombinant proteins to investigate this possibility and will use strategies similar to those employed for ERK. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPATIAL AND TEMPORAL CHARACTERISTICS OF CENTRAL PAIN SE Principal Investigator & Institution: Mauderli, Andre P.; Prosthodontics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: (provided by the applicant): Prolonged pain appears to have the potential to modulate its own intensity through positive and negative feedback (central sensitization by pain, pain inhibition by pain). If the feedback is positive, the result is a vicious pain cycle and a progressive increase in pain sensitivity. Increased pain sensitivity means that a given stimulus is perceived as more painful (hyperalgesia), or - in more extreme cases - that a previously non-painful stimulus becomes painful (allodynia). The vicious cycle may lead to sensitization beyond the topographical boundaries of the original pain, and thus it may render remote body regions more pain-prone. The result may be a snowball effect of progressive expansion of the painful area. There is evidence suggesting that the vicious cycle may be a pathophysiological factor in certain chronic pain diseases, including fibromyalgia syndrome (FMS), myofascial pain syndrome (MPS), and irritable bowel syndrome (IBS). This research is guided by 4 questions: 1) Does the intensity and duration of a persistent pain have an effect on how pain sensitivity changes over time? 2) Does the sensitizing effect of pain signals reach beyond the topographical location of the original pain focus? 3) Is it possible to interrupt the vicious pain cycle and allow the sensitized state to return to normal by temporarily silencing the local pain focus that presumably started the cycle? 4) Does the maintenance of the sensitized state depend on central NMDA receptor function, molecular constituents known to play a role in temporal integration of pain stimuli and other memory systems? The subjects in this study will be asked to rate pain intensities by setting the slider on an electronic visual analog scale. Novel methodology will be used for probing the temporal and spatial response properties of central pain modulation with experimental pain with prolonged series of thermal pulses. The effect of silencing clinical pain foci with transdermally delivered local anesthetics on thermallyinduced sensitization will be studied. The importance of NMDA receptor systems in the maintenance of a sensitized state will be
Studies
61
assessed by measuring pain sensitization properties before and after pharmacologically blocking them. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPINAL ACTION OF OPIATES Principal Investigator & Institution: Yaksh, Tony L.; Professor; Anesthesiology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-JUL-1983; Project End 31-MAY-2003 Summary: (ADAPTED FROM THE APPLICANT'S ABSTRACT) Hyperalgesic states result from the release of primary afferent transmitter release e.g., substance P (SP) from capsaicin-sensitive C fibers which activate postsynaptic systems through an NK1 receptor. This activation leads to the spinal release of excitatory amino acids and prostaglandins (PGE2), which evokes a facilitated state through an action on NMDA and prostanoid receptors. This hormonal input leads to phosphorylation of receptors and channels which can enhance nociceptive processing. Spinal mu opioid and alpha2 adrenergic agonists produce antinociception, in part by blockade at a site presynaptic to the primary afferent leading to a block of SP release and by an action at receptors postsynaptic to the primary afferent. Continued presence of the agonists results in an increase in the dose required by a probe drug to produce a given effect. When an antagonist is delivered to a tolerant system, withdrawal is observed which is associated with hyperalgesia. Accumulating evidence suggested that these effects, injury evoked hyperalgesia, spinal tolerance and withdrawal-evoked hyperalgesia are mediated through parallel changes in spinal NMDA receptor activity and changes in the phosphorylation state of spinal neurons induced by kinases/phosphatases activated during chronic afferent input and exposure to opiates. These observations provoke several hypotheses. 1) Inhibition by mu or alpha2 agonists of capsaicin-evoked release of SP from afferent terminals or release of glutamate and PGE2 evoked by local NK1 receptor activation from nonafferent spinal terminals will be diminished by continuous exposure to mu/alpha2; 2) After chronic exposure to spinal mu or alpha2 agonists, antagonists (withdrawal) will evoke hyperalgesia and enhance release of spinal SP, PGE2/ glutamate. 3) Concurrent spinal NMDA antagonism will prevent loss of effect by mu or alpha2 agonists on evoked release and prevent release observed in antagonistevoked withdrawal. 4) mu PKC) and phosphatases (e.g. calcineurin), which may decrease (by phosphorylation) or increase (by dephosphorylation) the ability of the agonist to reduce C transmitter release and nociception after chronic exposure. 5) Blockade of synthesis of specific kinases (PKCalpha or PKCgamma) and phosphatases (calcineurin) will reduce/enhance, respectively, tolerance and withdrawal-hyperalgesia. These studies will define i) the role of primary afferents in antinociception in the face of chronic opiate or alpha2 exposure; ii) linkages at which NMDA receptor antagonism alters spinal mu and alpha2 tolerance, and iii) the role of spinal isozymes (kinases and phosphatases) which regulate phosphorylation in the development of tolerance and hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SPINAL DYNORPHIN AND OPIOID TOLERANCE Principal Investigator & Institution: Porreca, Frank F.; Professor of Pharmacology and Anesthesio; Pharmacology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2003
62
Chronic Pain
Summary: One of the most significant health problems in our country is the inadequate treatment of chronic abnormal pains such as those associated with nerve injury or pathology (neuropathic pain). Inextricably linked to such chronic pains are the difficulties associated with the use of opioids for prolonged periods, where tolerance limits effectiveness. An unexplained clinical and experimental paradox is that the use of spinal opioids for chronic pain results not only in analgesic tolerance, but also in the development of abnormal pain (i.e., hyperesthesias including hyperalgesia and allodynia). Opioid tolerance and the post-nerve injury state have been suggested to be (mechanistically similar, at least at the spinal level. Blockade of the NMDA receptor has been shown to both prevent the development of, and reverse established, opioid tolerance as well as many of the behavioral consequences of experimental neuropathic pain. While such studies underscore the importance of the NMDA receptor in these processes, these pharmacological investigations have not identified the underlying endogenous spinal mechanisms which may promote opioid tolerance and the consequences of nerve injury through direct or indirect actions at the NMDA receptor. Like others, we have noted many similarities between the post-nerve injury state and spinal opioid tolerance and have discovered a multisegmental elevation of spinal dynorphin in both conditions. In both situations, blockade of the actions of elevated spinal dynorphin with antiserum to the peptide reestablishes opioid antinociceptive potency and efficacy and blocks abnormal pain. These observations lead us to hypothesize that (a) spinal opioid antinociceptive tolerance and the abnormal pain seen following spinal opioid administration are due, at least in part, to the non-opioid actions of elevated (i.e., pathological) levels of spinal dynorphin, and (b) prevention of dynorphin action, or expression, will reverse or prevent opioid tolerance and spinal opioid associated pain. This hypothesis will be tested by (i) evaluating intrathecal (i.th.) opioid agonist or antagonist- induced regulation of spinal dynorphin, (ii) pharmacological elevation of spinal dynorphin with i.th. infusion of dynorphin or the non-opioid peptide dynorphin(2-17), and (iii) prevention of the actions, or expression of, elevated levels of spinal dynorphin elicited by i.th. opioid infusion using antiserum to the peptide or antisense oligodeoxynucleotides to prodynorphin. It is hypothesized that enhancing spinal dynorphin levels either physiologically, or pharmacologically, will result in features common to opioid tolerance and to peripheral nerve injury (i.e., reduced antinociceptive actions of spinal opioids and abnormal response to sensory input including hyperalgesia and tactile allodynia), while blockade of endogenous dynorphin action or prevention of dynorphin expression will reverse or prevent opioid tolerance and related pain. Such experiments will establish whether the action or expression of dynorphin is critical for the development or maintenance of opioid antinociceptive tolerance and the abnormal pain produced by sustained spinal administration of opioids. The data from these studies will provide new insight on the possibility that dynorphin may be a crucial link in promoting opioid tolerance, reveal the regulation of spinal dynorphin expression by opioids, and provide a mechanistic basis for the paradoxical pain seen following spinal opioids in animals and in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPINAL NITRIC OXIDE IN CHRONIC INFLAMMATORY PAIN Principal Investigator & Institution: Roerig, Sandra C.; Professor; Pharmacology and Therapeutics; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2002 Summary: Untreated chronic pain leads to reorganization of neuronal circuits within the central nervous system (CNS), central sensitization, and enhanced pain. Chronic
Studies
63
pain patients are often depressed, with higher morbidity probability. In animal models of chronic inflammation, paw and joint inflammation is accompanied by both thermal and mechanical hyperalgesia as well as increased nitric oxide (NO) production in plasma and joint synovial tissue. Nitric oxide is synthesized from arginine by NO synthase (NOS) which is found in at least three isoforms, constitutive endothelial (ceNOS) and neuronal (cnNOS) and inducible (iNOS). Although a major source of increased NO in inflammation is likely due to activity of iNOS is peripheral cells involved in the immune response, increased NOS activity is also found in spinal cord, the first relay site for pain processing. The relative activities of spinal iNOS and cnNOS in inflammatory pain and their contributions to hyperalgesia and inflammation are not known. The proposed studies are designed to test the hypothesis that spinal cnNOS activity contributes to both the inflammation and the hyperalgesia observed in chronic inflammatory pain. Chronic inflammation will be induced by administration of peptidoglycan/polysaccharide (PG/PS) or complete Freund s adjuvant (CFA) into rats, treatments that produce chronic inflammation of the limbs. Specific aims are to (1) selectively inhibit activity of spinal cnNOS with selective inhibitors or antisense oligodeoxynucleotide (ODN) administered directly into the spinal cord and measuring peripheral inflammation and thermal and mechanical nociception. Expression of spinal cnNOS protein in spinal cord slices and dorsal root ganglia will be measured by immunocytochemistry at various time points during development and maintenance of inflammation. Total NOS activity is spinal cord homogenates will also be determined by measuring conversion of arginine to citrulline. These results will be compared to those obtained with spinal injection of missense ODN or vehicle. (2) develop a technique using a NO-sensitive microelectrode to measure real time in situ release of NO in the spinal cord of anesthetized rats. This technique will be used to measure spinal NO release following noxious mechanical stimulation of both inflamed and non-inflamed hindpaws. Effects of cnNOS inhibition on this release will be measured. Results of these studies will provide information about the role of spinal NO in initiation, development and maintenance or peripheral chronic inflammation and hyperalgesia. This information can be used to develop new drugs to treat chronic inflammatory pain or other types of chronic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES OF PAIN IN PATIENTS WITH INTERSTITIAL CYSTITIS Principal Investigator & Institution: Wesselmann, Ursula; Associate Professor; Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The long range objective of this research is to elucidate the pathophysiological mechanisms of pain in patients with interstitial cystitis (IC)in order to develop better strategies for alleviating chronic pain in these patients. IC shares many features with other chronic non-malignant visceral pain syndromes. In clinical practice much emphasis has been placed on finding a specific etiology and specific pathological markers for this disease and on identifying specific events that precipitate IC. This conceptualization has influenced clinical treatment approaches but has not resulted in significant progress so far. An additional approach is suggested, based on the conceptualization of three hypotheses: (1) a spectrum of different insults can lead to chronic visceral pain in patients suffering from IC, (2) different underlying pathogenic pain mechanisms may require different pain treatment strategies for patients diagnosed with IC, (2) different underlying pathogenic pain mechanisms may require different pain treatment strategies for patients diagnosed with IC, (3) multiple different
64
Chronic Pain
pathogenic pain mechanisms may coexist in the same patient, requiring several different pain treatment strategies (perhaps concomitantly) to successfully treat chronic visceral pain associated with IC. This conceptualization is likely to lead to new insights into the neurophysiological mechanisms of IC and to novel treatment avenues for patients suffering from IC. As a first step towards a better understanding of the neurophysiological mechanisms of chronic pain in patients with IC we propose to characterize pain in patients with IC in detail using quantitative sensory testing, taking advantage of the typical areas of referred visceral pain, which are easily accessible to quantitative sensory testing. We hypothesize that patients with IC can be differentiated into 3 main groups based on their "sensory profiles" as assessed with quantitative sensory testing and that treatment of pain in IC will be more effective, if based on recognition of the underlying neurophysiological mechanisms. These studies will give new insights into the central and peripheral mechanisms of chronic pain in patients with IC. The results of these studies may rapidly contribute to the design of treatment strategies specifically targeted at the underlying neural mechanisms of chronic pain in patients with IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TMD LONGITUDINAL STUDIES: CLINICAL/CHRONIC PAIN SYNDROME Principal Investigator & Institution: Leresche, Linda A.; Research Professor; Oral Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JAN-1989; Project End 31-AUG-2004 Summary: This application requests continuation of the Program Project TMD Longitudinal Studies: Clinical/Chronic Pain Syndromes. {{The overall goal is to conduct multi-disciplinary research aimed at understanding the onset course, and appropriate care of chronic, recurrent pain conditions, with particular emphasis on temporomandibular disorders (TMD).}} The project will continue to focus on TMD as a clinical entity, the adaptation of persons with pain to their pain problem and the interaction of pain patients with the health care delivery system. An inn integral part of the research strategy will continue to be comparison with TMD with other common chronic pain conditions, {{in order to understand the degree to which findings are related to specific clinical entries or are associated with chronic pain more generally.}} Project 1 will assess the prevalence and incidence of TMD pain, headache, back pain and abdominal pain in adolescents, and identify risk factors for onset of each of these pain complaints. The prevalence of headache and TMD pain is much higher in adult women than in men; the studies are designed to test the hypothesis that these prevalence differences begin in adolescence and are associated with the hormonal changes of puberty. Project 2 aims to increase scientific understanding of the mechanisms by which beliefs and coping strategies affect adjustment of patients with chronic, recurrent pain. The project will evaluate, through a randomized clinical trial, whether a brief intervention designed to change beliefs and coping strategies enhances outcomes of patients receiving TMD treatment. Project 3 seeks a more effective and cost-effective integrated of medical care and self-care for chronic, recurrent pain in primary care settings. The aims are identify improved methods for analysis of automated health care and medicine use data for TMD, back pain and headache patients and identify modifiable determinants lf long-term health care use; evaluate the impact of self-care groups on long term health care and medication use. Project 4 is a randomized clinical trial to evaluate whether supplementing usual TMD treatment with low cost stepped care interventions that education patients in self care improves patients' pain reduces
Studies
65
treatment seeking and improves functional status over time A Scientific Core will provide scientific direction, project coordination, data management/statistical support and shared scientific expertise. An Administrative ore will insure effective administration on the Program Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF ENDOMETRIOSIS-ASSOCIATED PELVIC PAIN Principal Investigator & Institution: Guzick, David S.; Professor and Chair; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Approximately one-third of women with chronic pelvic pain have endometriosis. Surgical treatment of endometriosis with laparoscopic excision of implants and lysis of adhesions is often successful in reducing pain in the short term. Furthermore, several postoperative medical treatments have been shown to be efficacious in maintaining pain reduction for as long as the medication is continued. After stopping the medication, however, the level of pain tends to trend upwards towards pre-treatment levels. The desired postoperative treatment is one that is can be used for a long period of time, so as to minimize the chance of pain recurrence. Simplicity of administration and cost-effectiveness are other desirable characteristics of an ideal postoperative regimen. The only FDA approved 12-month treatment for endometriosis-associated pain is a combination of leuprolide acetate (a GnRH analog), 11.25 mg IM q 12 weeks, and norethindrone acetate, 5 mg PO daily. Use of this regimen has been constrained by its complexity and cost. As an alternative, the continuous use of oral contraceptives has been advocated as a practical, inexpensive strategy for long-term medical treatment of endometriosis-associated pain. Although such an approach is frequently used in clinical practice, there has been no clinical trial of its efficacy. The goal of this project is to compare the efficacy and cost-effectiveness of continuous oral contraceptives and leuprolide+norethindrone in the postoperative treatment of endometriosis-associated pelvic pain. Investigators at the University of Rochester School of Medicine and Harvard Medical School will recruit 194 women for randomization to one of the two treatments, each of which will continue for 48 weeks. Randomization will occur after biopsy-proven endometriosis is established. Pelvic pain and quality-of-life assessments will be obtained at regular intervals. The recruitment goal is 88 subjects per arm after a 10% drop-our rate. Change scores for these measures will be compared between the two treatments. The study has 80% power to test non-inferiority of oral contraceptives at the 5% level of significance, using a 1-point difference in the change scores for pain as the threshold. In addition, a cost-effectiveness analysis will be performed by calculating the cost per unit reduction in pain score for each treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TREATMENT OF RECURRENT PAIN SYNDROMES IN CHILDREN Principal Investigator & Institution: Scharff, Lisa; Assistant Professsor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 21-JUN-1999; Project End 31-MAY-2004 Summary: Recurrent Pain Syndromes (RPS) are relatively common to pediatric populations. Two of the most common types of RPS are recurrent abdominal pain (RAP) and migraine. RAP and migraine are commonly thought to be provoked by similar factors (particularly stress), and similar patterns of pain are described in children with both types of RPS. A biobehavioral model has been proposed that relates precipitating,
66
Chronic Pain
intervening, and functional status factors in chronic and recurring pain in children. This model has not been extensively tested in children with different types of pain disorders. If one model is hypothesized to fit different pain complains, a variety of pediatric pain sufferers should be arrested and compared to that model. Multiple studies with adult pain patients have demonstrated that perceptions of pain are strongly influenced by various psychosocial variables that in turn influence each other. There is a severe lack of such research in pediatric populations. The proposed study will assess the fit of the biobehavioral model in children with RAP and migraine. The precipitating factor of stress will be assessed in the form of daily hassles, and intervening variables such as parental somatic symptoms, depression and anxiety (in both parents), family environment, social support, and stress coping strategies will be evaluated. Functional status variables will include measures of functional disability, depression, anxiety, behavior problems, and school attendance. The biobehavioral model will also be assessed in the form of a treatment addressing stress management strategies (the proposed participant of pain in the model). Non-medical treatment of migraine has demonstrated some success, with the majority of studies lacking adequate sample sizes or control groups. Studies examining treatment response in other types of RPS, such as RAP, is lacking. No studies have compared treatment response in different types of RPS to the same treatment. The proposed treatment study will compare a treatment including relaxation training, cognitive coping skills training, thermal biofeedback, and parent education to a hand-cooling biofeedback/supportive therapy control and a waist-list in children with RPS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRIGEMINAL NEUROPATHIC PAIN MECHANISMS Principal Investigator & Institution: Henry, Michael A.; Surgical Dentistry; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Chronic neuropathic pain can be a devastating disease and the management is often inadequate. A recent focus of pain research is examining changes in the expression of sodium channels that follow nerve injury since these changes may contribute to neuronal hyperexcitability and the development of neuropathic pain. This proposal will investigate the distributions of Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7, Nav1.8 and Nav1.9 sodium channel isoforms at both the light and electron microscopic levels in normal rat trigeminal primary afferents (infraorbital nerve, trigeminal ganglion/root entry zone and trigeminal sensory nucleus) and in intrinsic neurons in the trigeminal sensory nucleus. Once the normal expression is determined for each isoform, then changes in this expression will be evaluated in the same regions following a chromic suture injury to; 1) infraorbital nerve, or 2) trigeminal root entry zone, combined with behavioral testing for altered nociception. The hypothesis is that there will be a change in the normal distribution of the sodium channel isoforms following injury that correlates with behavioral evidence for altered nociception, the changes may depend on the site of the injury (peripheral vs. central), these changes contribute to neuronal hyperactivity of both primary afferents and intrinsic neurons seen following lesions, and the reduction of hyperexcitability with sodium channel blocking drugs. The trigeminal system represents an excellent model system to evaluate differences in sodium channel expression following either peripheral nerve or central root injury since distinct clinical entities are seen in humans following these different injuries. Trigeminal neuralgia may result from a root entry zone injury, while peripheral trigeminal neuropathy follows damage to peripheral nerves. There
Studies
67
may be a difference in the expression of sodium channels following peripheral and central injury, since patients with trigeminal neuralgia usually respond to carbamazepine, while patients with peripheral trigeminal neuropathy rarely obtain significant relief with only carbamazepine. A differential expression of sodium channels in different fiber types may also be responsible for the different clinical characteristics of pain seen following peripheral and central injury. Identification of specific sodium channel alterations after injury may help develop more selective treatments for neuropathic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VENTROCAUDAL THALAMUS IN HUMAN PAIN Principal Investigator & Institution: Lenz, Frederick A.; Professor; Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 10-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract): The proposal is a competing continuation of a subproject in an earlier program project grant (P01 NS32386). The studies aim at continuing the examination of the role of the human somatosensory thalamus (Vc) in pain. The long-term objective is to define the role of thalamic activity in signaling thermal sensations and pain sensations using a combination of neurophysiological and psychophysical techniques. Single unit recordings in Vc are performed in chronic pain patients and patients with movement disorders. Recordings in the latter group are considered as generating control data. Aim 1 examines the properties of spike trains in Vc to painful and nonpainful mechanical and thermal stimuli, in movement disorder patients. They also plan on testing whether the spike train properties change with changes in stimulus intensity and as a function of attention. Aim 2 examines the sensations evoked by electrical stimulation within Vc in movement disorder patients. They will examine the sensations as a function of temporal properties of stimuli in an effort to distinguish between paresthesias, warm, cool, & pain perceptions, and to determine the relationship between temporal patterns and intensity perception, as well as relate the stimulus pattern to the characteristics of the neuronal discharge with the equivalent sensation. Aim 3 examines the same questions as in aims 1 & 2 in the Vc of chronic pain patients to differentiate changes in coding properties between the two groups of subjects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: VIRTUAL REALITY ANALGESIA FOR REHABILITATION IN CHILDREN Principal Investigator & Institution: Sharar, Sam R.; Anesthesiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 03-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): One of the most frequent, yet challenging secondary problems experienced by children who require rehabilitation from disabling conditions is pain. Pain occurs at rest and/or with rehabilitation activities and arises in both chronic settings (e.g., cerebral palsy) and subacute settings (e.g., repetitive wound care and physical therapy during extended treatment of cutaneous burns). Conventional pharmacologic analgesic strategies, although widely used and efficacious in children with acute pain, are avoided in these chronic and subacute settings due to associated complication (e.g. tolerance) and lack of efficacy (development of central neuropathic pain syndromes). This project will explore two non-pharmacologic analgesic techniques
68
Chronic Pain
for children ages 8-20 years, emphasizing 1) virtual reality (VR) analgesia, a highly innovative technology with newly demonstrated efficacy in such settings, and 2) its novel combination with hypnosis. The analgesic mechanisms of VR and hypnosis are incompletely understood, although they share a common thread distraction of conscious attention from environmental stimuli, leaving less of this cognitive resource to devote to pain perception. The goal of this project is to develop a program that will effectively investigate the analgesic mechanisms and optimize the clinical use of VR and combined VR/hypnosis in disabled children with pain and/or who require rehabilitation activities. The specific aims of the project are 1) to develop an effective, multidisciplinary group capable of posing and answering appropriate study questions with tangible outcome measures, 2) to design and fabricate VR hardware ad software, and develop VR protocols necessary to address mechanistic questions and perform future clinical trials, and 3) to perform pilot clinical studies to assess the efficacy of repetitive application of VR, and to investigate the efficacy of and the interactions between VR and hypnosis when used simultaneously. The anticipated immediate benefits of this project include establishing the specialized research team and equipment necessary to perform future mechanistic studies and clinical trials of VR and VR/hypnosis, as well as collect pilot clinical data to direct future investigations. Long-term benefits include the establishment of indications and clinical protocols for the use of VR and/or hypnosis in the treatment of rehabilitation-induced and disability-related pain in this challenging patient population, with more widespread application to a variety of age groups, greater ease of use, and potential economic benefit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VULVODYNIA INTERVENTIONS
PREVALENCE
AND
EFFICACY
OF
4
Principal Investigator & Institution: Bachmann, Gloria A.; Ob, Gyn and Reproductive Scis; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 08854 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-AUG-2005 Summary: Vulvodynia is a complex, multi-factorial chronic pain syndrome which is associated with significant distress and interpersonal. Vulvar vestibulitis and dyspareunia are two common, although not well-understood clinical components or sub-types of vulvodynia. Chronic vulvar pain is experienced by, according to recent surveys, about 10-15% of the female population between 18 and 80. Pathophysiologic findings have not been convincing for the role of any specific antibody or etiological mechanism, although several have been proposed including aberrant somatosensory processing in the peripheral or central inflammatory process. The epidemiology and predictors of vulvodynia have similarly not been well- articulated in the literature. One study suggested that the disorder may be largely limited to white, middle-aged women, although sampling and data gathering limitations cloud the assessment of these findings. Thirdly, many centers have begun emphasizing surgical treatments for vulvar vestibulitis, although these approach is rejected by about 1/3 of women at the outset. The vestibulectomy procedure also leads to definite worsening of the condition in about 10% of cases. This grant will propose to examine efficacy, outcomes and costeffectiveness associated with four non-surgical interventions for vulvodynia. In general, the women's Health Research Section of RWJMS is committed to offering minimallyinvasive services and treatments to a broad diversity of women in the central northeast region. Our previous experience and that of our Co-PI's make our site uniquely wellprepared to offer a broad range of dissemination and educational experiences, both
Studies
69
locally and nationally, in the final years of the grant cycle. We plan to arrange and host an international consensus conference (something we have done twice recently in other areas of relevance), and to disseminate findings obtained from this and similar conferences broadly. We will also disseminate any questionnaires and treatment manuals developed in the context of this grant via website or other appropriate electronic or non-electronic form. We will develop patient education and public information materials, which will also be distributed in the most accessible and least costly form. Our ultimate goal is to share findings from this and related research with the broadest cross-spectrum of women that we can. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “chronic pain” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for chronic pain in the PubMed Central database: •
A comparison of the potential role of the tetrodotoxin-insensitive sodium channels, PN3 /SNS and NaN /SNS2, in rat models of chronic pain. by Porreca F, Lai J, Bian D, Wegert S, Ossipov MH, Eglen RM, Kassotakis L, Novakovic S, Rabert DK, Sangameswaran L, Hunter JC.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33594
•
Clinical practice guidelines for the care and treatment of breast cancer: the management of chronic pain in patients with breast cancer (summary of the 2001 update). by Emery C, Gallagher R, Hugi M, Levine M.; 2001 Oct 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81584
•
Opioids and chronic pain. by Russell AS, Aaron SL.; 2003 Oct 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=219619
•
Opioids and chronic pain. by Busse JW.; 2003 Oct 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=219618
•
Opioids and chronic pain. by Gardner-Nix J.; 2003 Oct 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=219620
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
70
Chronic Pain
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with chronic pain, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “chronic pain” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for chronic pain (hyperlinks lead to article summaries): •
A comparison of blacks and whites seeking treatment for chronic pain. Author(s): McCracken LM, Matthews AK, Tang TS, Cuba SL. Source: The Clinical Journal of Pain. 2001 September; 17(3): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587117&dopt=Abstract
•
A comparison of chronic pain between an urban and rural population. Author(s): Hoffman PK, Meier BP, Council JR. Source: Journal of Community Health Nursing. 2002 Winter; 19(4): 213-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494742&dopt=Abstract
•
A fourth empirically derived cluster of chronic pain patients based on the multidimensional pain inventory: evidence for repression within the dysfunctional group. Author(s): Burns JW, Kubilus A, Bruehl S, Harden RN. Source: Journal of Consulting and Clinical Psychology. 2001 August; 69(4): 663-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550732&dopt=Abstract
•
A pain neuromatrix approach to patients with chronic pain. Author(s): Moseley GL. Source: Manual Therapy. 2003 August; 8(3): 130-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909433&dopt=Abstract
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
Studies
71
•
A pain workshop: an approach to eliciting the views of young people with chronic pain. Author(s): Carter B, Lambrenos K, Thursfield J. Source: Journal of Clinical Nursing. 2002 November; 11(6): 753-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427180&dopt=Abstract
•
A preliminary study of multidimensional pain inventory profile differences in predicting treatment outcome in a heterogeneous cohort of patients with chronic pain. Author(s): Gatchel RJ, Noe CE, Pulliam C, Robbins H, Deschner M, Gajraj NM, Vakharia AS. Source: The Clinical Journal of Pain. 2002 May-June; 18(3): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048414&dopt=Abstract
•
A prospective one-year outcome study of interdisciplinary chronic pain management: compromising its efficacy by managed care policies. Author(s): Robbins H, Gatchel RJ, Noe C, Gajraj N, Polatin P, Deschner M, Vakharia A, Adams L. Source: Anesthesia and Analgesia. 2003 July; 97(1): 156-62, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818959&dopt=Abstract
•
A review of chronic pain after inguinal herniorrhaphy. Author(s): Poobalan AS, Bruce J, Smith WC, King PM, Krukowski ZH, Chambers WA. Source: The Clinical Journal of Pain. 2003 January-February; 19(1): 48-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514456&dopt=Abstract
•
A snapshot view of the impact of chronic pain on adolescents. Author(s): Matthews E. Source: British Journal of Nursing (Mark Allen Publishing). 2002 June 13-26; 11(11): 73544. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070375&dopt=Abstract
•
A systematic review of hydromorphone in acute and chronic pain. Author(s): Quigley C, Wiffen P. Source: Journal of Pain and Symptom Management. 2003 February; 25(2): 169-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590032&dopt=Abstract
•
Acupuncture, transcutaneous electrical nerve stimulation, and laser therapy in chronic pain. Author(s): Fargas-Babjak A. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S105-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783823&dopt=Abstract
72
Chronic Pain
•
Acute and chronic pain syndromes after thoracic surgery. Author(s): Hazelrigg SR, Cetindag IB, Fullerton J. Source: The Surgical Clinics of North America. 2002 August; 82(4): 849-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472133&dopt=Abstract
•
Acute vs. chronic pain. Author(s): Auvenshine RC. Source: Tex Dent J. 2000 July; 117(7): 14-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858059&dopt=Abstract
•
Adaptation to chronic pain in systemic lupus erythematosus: applicability of the multidimensional pain inventory. Author(s): Greco CM, Rudy TE, Manzi S. Source: Pain Medicine (Malden, Mass.). 2003 March; 4(1): 39-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873277&dopt=Abstract
•
Adjunctive agents in the management of chronic pain. Author(s): Guay DR. Source: Pharmacotherapy. 2001 September; 21(9): 1070-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560197&dopt=Abstract
•
Age-related differences in the qualities but not the intensity of chronic pain. Author(s): Gagliese L, Melzack R. Source: Pain. 2003 August; 104(3): 597-608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927632&dopt=Abstract
•
An age-based comparison of chronic pain clinic patients. Author(s): Wijeratne C, Shome S, Hickie I, Koschera A. Source: International Journal of Geriatric Psychiatry. 2001 May; 16(5): 477-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11376463&dopt=Abstract
•
An analysis of the influence of insurance sponsorship on MMPI changes among patients with chronic pain. Author(s): Fow NR, Dorris G, Sittig M, Smith-Seemiller L. Source: Journal of Clinical Psychology. 2002 July; 58(7): 827-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205722&dopt=Abstract
•
An experimental study of attention, labelling and memory in people suffering from chronic pain. Author(s): Rode S, Salkovskis PM, Jack T. Source: Pain. 2001 November; 94(2): 193-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11690733&dopt=Abstract
Studies
73
•
Analgesic effects of dextromethorphan and morphine in patients with chronic pain. Author(s): Heiskanen T, Hartel B, Dahl ML, Seppala T, Kalso E. Source: Pain. 2002 April; 96(3): 261-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972998&dopt=Abstract
•
Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: a multicenter, randomized, double-blind, placebo-controlled trial. Author(s): Sittl R, Griessinger N, Likar R. Source: Clinical Therapeutics. 2003 January; 25(1): 150-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637117&dopt=Abstract
•
Anxiety sensitivity in the prediction of pain-related fear and anxiety in a heterogeneous chronic pain population. Author(s): Zvolensky MJ, Goodie JL, McNeil DW, Sperry JA, Sorrell JT. Source: Behaviour Research and Therapy. 2001 June; 39(6): 683-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400712&dopt=Abstract
•
Approaches to treatment decisions for psychiatric comorbidity in the management of the chronic pain patient. Author(s): Fishbain DA. Source: The Medical Clinics of North America. 1999 May; 83(3): 737-60, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10386123&dopt=Abstract
•
Assessing chronic pain in cognitively impaired elderly adults. Author(s): Verheul K. Source: Nursingconnections. 2000 Summer; 13(2): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12016665&dopt=Abstract
•
Assessment and management of chronic pain in elderly people. Author(s): Mitchell C. Source: British Journal of Nursing (Mark Allen Publishing). 2001 March 8-21; 10(5): 296304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170672&dopt=Abstract
•
Assessment of chronic pain behaviour: reliability of the method and its relationship with perceived disability, physical impairment and function. Author(s): Koho P, Aho S, Watson P, Hurri H. Source: Journal of Rehabilitation Medicine : Official Journal of the Uems European Board of Physical and Rehabilitation Medicine. 2001 March; 33(3): 128-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11482353&dopt=Abstract
74
Chronic Pain
•
Assessment of pain cognitions in cancer patients with chronic pain. Author(s): de Wit R, van Dam F, Litjens MJ, Abu-Saad HH. Source: Journal of Pain and Symptom Management. 2001 November; 22(5): 911-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728794&dopt=Abstract
•
Attendance at a pain clinic with severe chronic pain after open and laparoscopic inguinal hernia repairs. Author(s): Hindmarsh AC, Cheong E, Lewis MP, Rhodes M. Source: The British Journal of Surgery. 2003 September; 90(9): 1152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945086&dopt=Abstract
•
Balloon kyphoplasty: one-year outcomes in vertebral body height restoration, chronic pain, and activity levels. Author(s): Ledlie JT, Renfro M. Source: Journal of Neurosurgery. 2003 January; 98(1 Suppl): 36-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546386&dopt=Abstract
•
Barriers to managing chronic pain of older adults with arthritis. Author(s): Davis GC, Hiemenz ML, White TL. Source: Journal of Nursing Scholarship : an Official Publication of Sigma Theta Tau International Honor Society of Nursing / Sigma Theta Tau. 2002; 34(2): 121-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078535&dopt=Abstract
•
Behavioral and cognitive-behavioral treatment for chronic pain: outcome, predictors of outcome, and treatment process. Author(s): McCracken LM, Turk DC. Source: Spine. 2002 November 15; 27(22): 2564-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435995&dopt=Abstract
•
Behaviour-focused pain coping: consistency and convergence to work capability of the swedish version of the chronic pain coping inventory. Author(s): Ektor-Andersen J, Orbaek P, Isacsson SO; Malmo Shoulder-Neck Study Group. Source: Journal of Rehabilitation Medicine : Official Journal of the Uems European Board of Physical and Rehabilitation Medicine. 2002 January; 34(1): 33-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900260&dopt=Abstract
•
Biopsychosocial approaches to the treatment of chronic pain. Author(s): Nielson WR, Weir R. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S114-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783824&dopt=Abstract
Studies
75
•
Botulinum toxin type A therapy in chronic pain disorders. Author(s): Lang AM. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S69-73; Quiz S74-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708561&dopt=Abstract
•
Central hypersensitivity in chronic pain after whiplash injury. Author(s): Curatolo M, Petersen-Felix S, Arendt-Nielsen L, Giani C, Zbinden AM, Radanov BP. Source: The Clinical Journal of Pain. 2001 December; 17(4): 306-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783810&dopt=Abstract
•
Chronic pain and its management in primary care. Author(s): Smith L. Source: Southern Medical Journal. 2002 January; 95(1): 108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827242&dopt=Abstract
•
Chronic pain and the concept of disablement. Author(s): Hunter J. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S10-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783822&dopt=Abstract
•
Chronic pain in adolescents: evaluation of a programme of interdisciplinary cognitive behaviour therapy. Author(s): Eccleston C, Malleson PN, Clinch J, Connell H, Sourbut C. Source: Archives of Disease in Childhood. 2003 October; 88(10): 881-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500306&dopt=Abstract
•
Chronic pain in childhood and the medical encounter: professional ventriloquism and hidden voices. Author(s): Carter B. Source: Qualitative Health Research. 2002 January; 12(1): 28-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11797923&dopt=Abstract
•
Chronic pain in the workplace. Author(s): Faucett J, McCarthy D. Source: Nurs Clin North Am. 2003 September; 38(3): 509-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567206&dopt=Abstract
76
Chronic Pain
•
Chronic pain management and the surgeon: barriers and opportunities. Author(s): Lee KF, Ray JB, Dunn GP. Source: Journal of the American College of Surgeons. 2001 December; 193(6): 689-701; Discussion 701-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768686&dopt=Abstract
•
Chronic pain management in older people. Author(s): Helme RD. Source: European Journal of Pain (London, England). 2001; 5 Suppl A: 31-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798215&dopt=Abstract
•
Chronic pain, chronic stress and depression: coincidence or consequence? Author(s): Blackburn-Munro G, Blackburn-Munro RE. Source: Journal of Neuroendocrinology. 2001 December; 13(12): 1009-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722697&dopt=Abstract
•
Chronic pain, substance abuse and addiction. Author(s): Compton P, Athanasos P. Source: Nurs Clin North Am. 2003 September; 38(3): 525-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567207&dopt=Abstract
•
Chronic pain. Author(s): Finlay I, Hampson J, Fyrth K, Chamberlain S. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2001 December; 51(473): 1014. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766854&dopt=Abstract
•
Chronic pain. Author(s): Quinn MJ. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2001 December; 51(473): 1013-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766853&dopt=Abstract
•
Chronic pain: challenges and assessment strategies. Author(s): Herr K. Source: Journal of Gerontological Nursing. 2002 January; 28(1): 20-7; Quiz 54-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11829221&dopt=Abstract
Studies
77
•
Clinical practice guidelines for the care and treatment of breast cancer: the management of chronic pain in patients with breast cancer (summary of the 2001 update). Author(s): Emery C, Gallagher R, Hugi M, Levine M; Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 October 30; 165(9): 1218-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706911&dopt=Abstract
•
Combining somatic and psychosocial treatment for chronic pain patients: perhaps 1 + 1 does = 3. Author(s): Turk DC. Source: The Clinical Journal of Pain. 2001 December; 17(4): 281-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783807&dopt=Abstract
•
Compensation and chronic pain. Author(s): Teasell RW. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S46-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783831&dopt=Abstract
•
Complementary and alternative therapies: what is their place in the management of chronic pain? Author(s): Snyder M, Wieland J. Source: Nurs Clin North Am. 2003 September; 38(3): 495-508. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567205&dopt=Abstract
•
Comprehensive analysis and management of chronic pain. Author(s): Arnstein P. Source: Nurs Clin North Am. 2003 September; 38(3): 403-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567199&dopt=Abstract
•
Conscious and automatic uses of memory in chronic pain patients. Author(s): Grisart JM, Van der Linden M. Source: Pain. 2001 December; 94(3): 305-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731067&dopt=Abstract
•
Control of non-malignant chronic pain conditions in Japan and the possible future role of tramadol. Author(s): Itoh T. Source: European Journal of Pain (London, England). 2001; 5 Suppl A: 87-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798225&dopt=Abstract
78
Chronic Pain
•
Decreased levels of N-acetylaspartate in dorsolateral prefrontal cortex in a case of intractable severe sympathetically mediated chronic pain (complex regional pain syndrome, type I). Author(s): Grachev ID, Thomas PS, Ramachandran TS. Source: Brain and Cognition. 2002 June; 49(1): 102-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027396&dopt=Abstract
•
Decreased perfusion of the bilateral thalami in patients with chronic pain detected by Tc-99m-ECD SPECT with statistical parametric mapping. Author(s): Nakabeppu Y, Nakajo M, Gushiken T, Tsuchimochi S, Tani A, Kanmura Y. Source: Ann Nucl Med. 2001 October; 15(5): 459-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758955&dopt=Abstract
•
Demographic variables and chronic pain. Author(s): Hunter J. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S14-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783826&dopt=Abstract
•
Depression predicts disability in long-term chronic pain patients. Author(s): Ericsson M, Poston WS, Linder J, Taylor JE, Haddock CK, Foreyt JP. Source: Disability and Rehabilitation. 2002 April 15; 24(6): 334-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017467&dopt=Abstract
•
Development of a nurse-led chronic pain clinic in UK primary care. Author(s): Glasgow AC, Glasgow JA. Source: Int J Clin Pract. 2002 January-February; 56(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833551&dopt=Abstract
•
Dextromethorphan in chronic pain: a disappointing update. Author(s): Ben-Abraham R, Weinbroum AA. Source: Isr Med Assoc J. 2000 September; 2(9): 708-10. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11062774&dopt=Abstract
•
Diagnostic nerve blocks in chronic pain. Author(s): Bogduk N. Source: Best Pract Res Clin Anaesthesiol. 2002 December; 16(4): 565-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516892&dopt=Abstract
Studies
79
•
Differences on the projective hand test among chronic pain patients reporting three different pain experiences. Author(s): Panek PE, Skowronski JJ, Wagner EE. Source: Journal of Personality Assessment. 2002 October; 79(2): 235-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425388&dopt=Abstract
•
Differential effects of expressive anger regulation on chronic pain intensity in CRPS and non-CRPS limb pain patients. Author(s): Bruehl S, Chung OY, Burns JW. Source: Pain. 2003 August; 104(3): 647-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927637&dopt=Abstract
•
Differential relationships between anxiety and treatment-associated pain reduction among male and female chronic pain patients. Author(s): Edwards R, Augustson E, Fillingim R. Source: The Clinical Journal of Pain. 2003 July-August; 19(4): 208-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840614&dopt=Abstract
•
Disability and chronic pain after open mesh and laparoscopic inguinal hernia repair. Author(s): Bozuk M, Schuster R, Stewart D, Hicks K, Greaney G, Waxman K. Source: The American Surgeon. 2003 October; 69(10): 839-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570359&dopt=Abstract
•
Disrupted sleep patterns and daily functioning in patients with chronic pain. Author(s): McCracken LM, Iverson GL. Source: Pain Res Manag. 2002 Summer; 7(2): 75-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185371&dopt=Abstract
•
Dissociating anxiety from pain: mapping the neuronal marker N-acetyl aspartate to perception distinguishes closely interrelated characteristics of chronic pain. Author(s): Grachev ID, Fredickson BE, Apkarian AV. Source: Molecular Psychiatry. 2001 May; 6(3): 256-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11326290&dopt=Abstract
•
Do absorbable mesh sutures cause less chronic pain than nonabsorbable sutures after Lichtenstein inguinal herniorraphy? Author(s): Paajanen H. Source: Hernia : the Journal of Hernias and Abdominal Wall Surgery. 2002 March; 6(1): 26-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090577&dopt=Abstract
80
Chronic Pain
•
Do changes in cognitive factors influence outcome following multidisciplinary treatment for chronic pain? A cross-lagged panel analysis. Author(s): Burns JW, Kubilus A, Bruehl S, Harden RN, Lofland K. Source: Journal of Consulting and Clinical Psychology. 2003 February; 71(1): 81-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602428&dopt=Abstract
•
Does chronic pain predict future psychological distress? Author(s): McBeth J, Macfarlane GJ, Silman AJ. Source: Pain. 2002 April; 96(3): 239-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972995&dopt=Abstract
•
Does pain relief improve pain behavior and mood in chronic pain patients? Author(s): Sator-Katzenschlager SM, Schiesser AW, Kozek-Langenecker SA, Benetka G, Langer G, Kress HG. Source: Anesthesia and Analgesia. 2003 September; 97(3): 791-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933404&dopt=Abstract
•
Does personality or psychopathology predict disability in chronic pain patients? Author(s): Linder J, Poston WS 2nd, Haddock CK, Foreyt JP, Ericsson M. Source: Disability and Rehabilitation. 2000 April 15; 22(6): 281-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10864131&dopt=Abstract
•
Does sex make a difference in the prescription of treatments and the adaptation to chronic pain by cancer and non-cancer patients? Author(s): Turk DC, Okifuji A. Source: Pain. 1999 August; 82(2): 139-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467919&dopt=Abstract
•
Drug infusions for the diagnosis and treatment of chronic pain. Author(s): O'Gorman DA, Raja SN. Source: Current Pain and Headache Reports. 2002 December; 6(6): 452-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413404&dopt=Abstract
•
Economic evaluation of multidisciplinary pain management in chronic pain patients: a qualitative systematic review. Author(s): Thomsen AB, Sorensen J, Sjogren P, Eriksen J. Source: Journal of Pain and Symptom Management. 2001 August; 22(2): 688-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495715&dopt=Abstract
Studies
81
•
Effects of intermediate- and long-term use of opioids on cognition in patients with chronic pain. Author(s): Chapman SL, Byas-Smith MG, Reed BA. Source: The Clinical Journal of Pain. 2002 July-August; 18(4 Suppl): S83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479258&dopt=Abstract
•
Efficacy of a self-management group intervention for elderly persons with chronic pain. Author(s): Ersek M, Turner JA, McCurry SM, Gibbons L, Kraybill BM. Source: The Clinical Journal of Pain. 2003 May-June; 19(3): 156-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792554&dopt=Abstract
•
Electroconvulsive therapy in the management of chronic pain. Author(s): Rasmussen KG, Rummans TA. Source: Current Pain and Headache Reports. 2002 February; 6(1): 17-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11749873&dopt=Abstract
•
Electronic diaries for monitoring chronic pain: 1-year validation study. Author(s): Jamison RN, Raymond SA, Levine JG, Slawsby EA, Nedeljkovic SS, Katz NP. Source: Pain. 2001 April; 91(3): 277-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275385&dopt=Abstract
•
EMDR in the treatment of chronic pain. Author(s): Grant M, Threlfo C. Source: Journal of Clinical Psychology. 2002 December; 58(12): 1505-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455018&dopt=Abstract
•
Emerging trends in the pharmacotherapy of chronic pain. Author(s): Nitu AN, Wallihan R, Skljarevski V, Ramadan NM. Source: Expert Opinion on Investigational Drugs. 2003 April; 12(4): 545-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665411&dopt=Abstract
•
Employment-related factors in chronic pain and chronic pain disability. Author(s): Teasell RW, Bombardier C. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S39-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783830&dopt=Abstract
•
Encountering the continuing challenges for women with chronic pain: recovery through recognition. Author(s): Werner A, Steihaug S, Malterud K. Source: Qualitative Health Research. 2003 April; 13(4): 491-509. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703412&dopt=Abstract
82
Chronic Pain
•
Ethical considerations for neurologists in the management of chronic pain. Author(s): Holmlund T. Source: Neurology. 2002 August 13; 59(3): 473-4; Author Reply 474. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177397&dopt=Abstract
•
Ethical perspectives: opioid treatment of chronic pain in the context of addiction. Author(s): Cohen MJ, Jasser S, Herron PD, Margolis CG. Source: The Clinical Journal of Pain. 2002 July-August; 18(4 Suppl): S99-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479260&dopt=Abstract
•
Etiology, prevention, treatment, and disability management of chronic pain. Introduction. Author(s): Smith B, Gribbin M. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783821&dopt=Abstract
•
Etoricoxib in the treatment of chronic pain. Author(s): Duncan MR, Capell HA. Source: Int J Clin Pract. 2003 May; 57(4): 315-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800464&dopt=Abstract
•
Evaluating Snoezelen for relaxation within chronic pain management. Author(s): Schofield P. Source: British Journal of Nursing (Mark Allen Publishing). 2002 June 27-July 10; 11(12): 812-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131831&dopt=Abstract
•
Evaluation of a randomized preventive behavioural medicine work site intervention for public health workers at risk for developing chronic pain. Author(s): Dahl JC, Nilsson A. Source: European Journal of Pain (London, England). 2001; 5(4): 421-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743708&dopt=Abstract
•
Evolution of a rational use of opioids in chronic pain. Author(s): O'Callaghan JP. Source: European Journal of Pain (London, England). 2001; 5 Suppl A: 21-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798213&dopt=Abstract
Studies
83
•
Examinations of chronic pain and affect relationships: applications of a dynamic model of affect. Author(s): Zautra A, Smith B, Affleck G, Tennen H. Source: Journal of Consulting and Clinical Psychology. 2001 October; 69(5): 786-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11680555&dopt=Abstract
•
Exercise in the treatment of chronic pain. Author(s): Mior S. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S77-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783835&dopt=Abstract
•
Exercise prescription for older adults with osteoarthritis pain: consensus practice recommendations. A supplement to the AGS Clinical Practice Guidelines on the management of chronic pain in older adults. Author(s): American Geriatrics Society Panel on Exercise and Osteoarthritis. Source: Journal of the American Geriatrics Society. 2001 June; 49(6): 808-23. Review. Erratum In: J Am Geriatr Soc 2001 October; 49(10): 1400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480416&dopt=Abstract
•
Ezzo et al.: Is acupuncture effective for the treatment of chronic pain? A systematic review, PAIN 86(2000)217-225. Author(s): Mendelson G. Source: Pain. 2001 August; 93(2): 198-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486756&dopt=Abstract
•
Factors associated with analgesic and psychotropic medications use by communitydwelling older people with chronic pain. Author(s): Kung F, Gibson SJ, Helme RD. Source: Aust N Z J Public Health. 1999 October; 23(5): 471-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10575767&dopt=Abstract
•
Feasibility of fitness tests in subjects with chronic pain (fibromyalgia): discordance between cycling and 2-km walking tests. Author(s): Viitanen JV. Source: Rheumatology International. 2001 September; 21(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678295&dopt=Abstract
•
From chronic pain patient to peer: benefits and risks of volunteering. Author(s): Arnstein P, Vidal M, Wells-Federman C, Morgan B, Caudill M. Source: Pain Management Nursing : Official Journal of the American Society of Pain Management Nurses. 2002 September; 3(3): 94-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198640&dopt=Abstract
84
Chronic Pain
•
From confrontation to collaboration: collegial accountability and the expanding role of pharmacists in the management of chronic pain. Author(s): Brushwood DB. Source: The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics. 2001 Spring; 29(1): 69-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521273&dopt=Abstract
•
From hospital to home care: a randomized controlled trial of a Pain Education Programme for cancer patients with chronic pain. Author(s): de Wit R, van Dam F. Source: Journal of Advanced Nursing. 2001 December; 36(6): 742-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11903704&dopt=Abstract
•
From lesion to metaphor: chronic pain in British, French and German medical writings, 1800-1914. Author(s): Hodgkiss A. Source: Clio Medica (Amsterdam, Netherlands). 2000; 58: I-Iii, 1-218. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11027065&dopt=Abstract
•
Functional abnormalities of the cervical cord and lower medulla and their effect on pain: observations in chronic pain patients with incidental mild Chiari I malformation and moderate to severe cervical cord compression. Author(s): Thimineur M, Kitaj M, Kravitz E, Kalizewski T, Sood P. Source: The Clinical Journal of Pain. 2002 May-June; 18(3): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048419&dopt=Abstract
•
Functional assessment in patients with chronic pain: can physicians predict performance? Author(s): Walker WC, Cifu DX, Gardner M, Keyser-Marcus L. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2001 March; 80(3): 162-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11237269&dopt=Abstract
•
Functional self-efficacy and pain-related disability among older veterans with chronic pain in a primary care setting. Author(s): Barry LC, Guo Z, Kerns RD, Duong BD, Reid MC. Source: Pain. 2003 July; 104(1-2): 131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855322&dopt=Abstract
Studies
85
•
Further evaluation of the pain stages of change questionnaire: is the transtheoretical model of change useful for patients with chronic pain? Author(s): Jensen MP, Nielson WR, Romano JM, Hill ML, Turner JA. Source: Pain. 2000 June; 86(3): 255-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812255&dopt=Abstract
•
Gabapentin for chronic pain in spinal cord injury: a case report. Author(s): Kapadia NP, Harden N. Source: Archives of Physical Medicine and Rehabilitation. 2000 October; 81(10): 1439-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11030514&dopt=Abstract
•
Gender differences in associations between trauma history and adjustment among chronic pain patients. Author(s): Spertus IL, Burns J, Glenn B, Lofland K, McCracken L. Source: Pain. 1999 July; 82(1): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10422665&dopt=Abstract
•
Generalizing from a controlled trial: the effects of patient preference versus randomization on the outcome of inpatient versus outpatient chronic pain management. Author(s): de C Williams AC, Nicholas MK, Richardson PH, Pither CE, Fernandes J. Source: Pain. 1999 October; 83(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10506672&dopt=Abstract
•
Guidelines promote COX-2 inhibitors for managing chronic pain. Author(s): Young D. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 July 15; 59(14): 1315-6, 1318. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132552&dopt=Abstract
•
Has basic research contributed to chronic pain treatment? Author(s): Jensen TS, Gottrup H, Kasch H, Nikolajsen L, Terkelsen AJ, Witting N. Source: Acta Anaesthesiologica Scandinavica. 2001 October; 45(9): 1128-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683664&dopt=Abstract
•
Headache and other types of chronic pain. Author(s): Marcus DA. Source: Headache. 2003 January; 43(1): 49-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864758&dopt=Abstract
86
Chronic Pain
•
Health status of patients with chronic pain attending a pain center. Author(s): Wilkes LM, Castro M, Mohan S, Sundaraj SR, Noore F. Source: Pain Management Nursing : Official Journal of the American Society of Pain Management Nurses. 2003 June; 4(2): 70-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836151&dopt=Abstract
•
Here today and not gone tomorrow: the curse of chronic pain and other central sensitization syndromes. Author(s): Stahl SM. Source: The Journal of Clinical Psychiatry. 2003 August; 64(8): 863-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926998&dopt=Abstract
•
High risk model of threat perception in chronic pain patients: implications for primary care and chronic pain programs. Author(s): Kermit K, Devine DA, Tatman SM. Source: The Journal of Nervous and Mental Disease. 2000 September; 188(9): 577-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11009330&dopt=Abstract
•
Histological findings after long-term infusion of intrathecal ketamine for chronic pain: a case report. Author(s): Stotz M, Oehen HP, Gerber H. Source: Journal of Pain and Symptom Management. 1999 September; 18(3): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517045&dopt=Abstract
•
How can we learn to live with pain? A Q-methodological analysis of the diverse understandings of acceptance of chronic pain. Author(s): Risdon A, Eccleston C, Crombez G, McCracken L. Source: Social Science & Medicine (1982). 2003 January; 56(2): 375-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473322&dopt=Abstract
•
How do we manage chronic pain? Author(s): Schaible HG, Vanegas H. Source: Bailliere's Best Practice & Research. Clinical Rheumatology. 2000 December; 14(4): 797-811. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092803&dopt=Abstract
•
Hydromorphone for acute and chronic pain. Author(s): Quigley C. Source: Cochrane Database Syst Rev. 2002; (1): Cd003447. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869661&dopt=Abstract
Studies
87
•
Identification of obstacles for chronic pain patients to return to work: evaluation of a questionnaire. Author(s): Marhold C, Linton SJ, Melin L. Source: Journal of Occupational Rehabilitation. 2002 June; 12(2): 65-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014227&dopt=Abstract
•
Impact of experimentally-induced expectancy on the analgesic efficacy of tramadol in chronic pain patients: a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial. Author(s): de Craen AJ, Lampe-Schoenmaeckers AJ, Kraal JW, Tijssen JG, Kleijnen J. Source: Journal of Pain and Symptom Management. 2001 March; 21(3): 210-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11239740&dopt=Abstract
•
Improving the quality of pain treatment by a tailored pain education programme for cancer patients in chronic pain. Author(s): de Wit R, van Dam F, Loonstra S, Zandbelt L, van Buuren A, van der Heijden K, Leenhouts G, Duivenvoorden H, Huijer Abu-Saad H. Source: European Journal of Pain (London, England). 2001; 5(3): 241-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558980&dopt=Abstract
•
Incidence of chronic pain after minimal-invasive surgery for spontaneous pneumothorax. Author(s): Passlick B, Born C, Sienel W, Thetter O. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2001 March; 19(3): 355-8; Discussion 358-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251279&dopt=Abstract
•
Incomplete response to endoscopic sphincterotomy in patients with sphincter of Oddi dysfunction: evidence for a chronic pain disorder. Author(s): Linder JD, Klapow JC, Linder SD, Wilcox CM. Source: The American Journal of Gastroenterology. 2003 August; 98(8): 1738-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907327&dopt=Abstract
•
Indications and outcomes of reconstructive surgery in chronic pain of spinal origin. Author(s): Slosar PJ. Source: Spine. 2002 November 15; 27(22): 2555-62; Discussion 2563. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435993&dopt=Abstract
•
Information processing biases among chronic pain patients and ankylosing spondylitis patients: the impact of diagnosis. Author(s): Wells HJ, Pincus T, McWilliams E. Source: European Journal of Pain (London, England). 2003; 7(2): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600791&dopt=Abstract
88
Chronic Pain
•
Injections and surgical therapy in chronic pain. Author(s): Bernstein RM. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S94-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783838&dopt=Abstract
•
Integrative group therapy outcome related to psychosocial characteristics in patients with chronic pain. Author(s): Talo S, Forssell H, Heikkonen S, Puukka P. Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 2001 March; 24(1): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302461&dopt=Abstract
•
Intercostal nerve block with 5% tetracaine for chronic pain syndromes. Author(s): Doi K, Nikai T, Sakura S, Saito Y. Source: Journal of Clinical Anesthesia. 2002 February; 14(1): 39-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880021&dopt=Abstract
•
Interventions in chronic pain management. 1. Pain concepts, assessment, and medicolegal issues. Author(s): Lacerte M, Shah RV. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S35-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708556&dopt=Abstract
•
Interventions in chronic pain management. 2. New frontiers: invasive nonsurgical interventions. Author(s): Shah RV, Ericksen JJ, Lacerte M. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S39-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708557&dopt=Abstract
•
Interventions in chronic pain management. 3. New frontiers in pain management: complementary techniques. Author(s): Braverman DL, Ericken JJ, Shah RV, Franklin DJ. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S45-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708558&dopt=Abstract
Studies
89
•
Interventions in chronic pain management. 4. Medications in pain management. Author(s): Ericksen JJ, Braverman DL, Shah RV. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S50-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708559&dopt=Abstract
•
Interventions in chronic pain management. 5. Disease-specific issues in chronic pain. Author(s): Rashbaum IG, Lacerte M, Braverman DL, Ericksen JJ. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S57-62; Quiz S63-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708560&dopt=Abstract
•
Intrathecal pumps for giving opioids in chronic pain: a systematic review. Author(s): Williams JE, Louw G, Towlerton G. Source: Health Technology Assessment (Winchester, England). 2000; 4(32): Iii-Iv, 1-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173307&dopt=Abstract
•
Intrathecal therapy for chronic pain. Author(s): Miles J. Source: Stereotactic and Functional Neurosurgery. 2001; 77(1-4): 156-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378067&dopt=Abstract
•
Is acupuncture effective in treating chronic pain after spinal cord injury? Author(s): Nayak S, Shiflett SC, Schoenberger NE, Agostinelli S, Kirshblum S, Averill A, Cotter AC. Source: Archives of Physical Medicine and Rehabilitation. 2001 November; 82(11): 157886. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689979&dopt=Abstract
•
Is all chronic pain the same? A 25-year follow-up study. Author(s): Croft P, Lewis M, Hannaford P. Source: Pain. 2003 September; 105(1-2): 309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499449&dopt=Abstract
•
It is hard work behaving as a credible patient: encounters between women with chronic pain and their doctors. Author(s): Werner A, Malterud K. Source: Social Science & Medicine (1982). 2003 October; 57(8): 1409-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927471&dopt=Abstract
90
Chronic Pain
•
Kv1.1 channels of dorsal root ganglion neurons are inhibited by n-butyl-paminobenzoate, a promising anesthetic for the treatment of chronic pain. Author(s): Beekwilder JP, O'Leary ME, van den Broek LP, van Kempen GT, Ypey DL, van den Berg RJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 February; 304(2): 531-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538804&dopt=Abstract
•
Learned maintenance of pain: muscle tension reduces central nervous system processing of painful stimulation in chronic and subchronic pain patients. Author(s): Knost B, Flor H, Birbaumer N, Schugens MM. Source: Psychophysiology. 1999 November; 36(6): 755-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554589&dopt=Abstract
•
Lidocaine patch 5% and the management of chronic pain. Author(s): Argoff CE. Source: Southern Medical Journal. 2002 July; 95(7): 781. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144092&dopt=Abstract
•
Lifetime physical and sexual abuse in chronic pain patients: psychosocial correlates and treatment outcomes. Author(s): Bailey BE, Freedenfeld RN, Kiser RS, Gatchel RJ. Source: Disability and Rehabilitation. 2003 April 8; 25(7): 331-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745957&dopt=Abstract
•
Linking chronic pain and depression. Author(s): Gray E. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2001 March 7-13; 15(25): 33-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211823&dopt=Abstract
•
Living with chronic pain: the patient's perspective. Author(s): McHugh G, Thoms G. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2001 September 12-18; 15(52): 33-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205856&dopt=Abstract
•
Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia. Author(s): McCarberg BH, Barkin RL. Source: American Journal of Therapeutics. 2001 May-June; 8(3): 181-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344385&dopt=Abstract
Studies
91
•
Long-term outcomes during treatment of chronic pain with intrathecal clonidine or clonidine/opioid combinations. Author(s): Ackerman LL, Follett KA, Rosenquist RW. Source: Journal of Pain and Symptom Management. 2003 July; 26(1): 668-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850649&dopt=Abstract
•
Loss of nerve: a molecular approach to better treatment of chronic pain. Author(s): Friedrich MJ. Source: Jama : the Journal of the American Medical Association. 2000 January 12; 283(2): 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634324&dopt=Abstract
•
Low calcitonin gene-related, peptide-like immunoreactivity in cerebrospinal fluid from chronic pain patients. Author(s): Lindh C, Liu Z, Welin M, Ordeberg G, Nyberg F. Source: Neuropeptides. 1999 December; 33(6): 517-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10657534&dopt=Abstract
•
Major depression and insomnia in chronic pain. Author(s): Wilson KG, Eriksson MY, D'Eon JL, Mikail SF, Emery PC. Source: The Clinical Journal of Pain. 2002 March-April; 18(2): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882770&dopt=Abstract
•
Management of cancer-related and noncancer-related chronic pain in Connecticut: successes and failures. Author(s): Tarzian AJ, Davidson SM, Hoffmann DE. Source: Conn Med. 2002 November; 66(11): 683-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476511&dopt=Abstract
•
Management of chronic pain in whiplash injury. Author(s): Kwan O, Friel J. Source: The Journal of Bone and Joint Surgery. British Volume. 2003 August; 85(6): 931; Author Reply 931-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931821&dopt=Abstract
•
Management of chronic pain in whiplash injury. Author(s): Alpar EK, Onuoha G, Killampalli VV, Waters R. Source: The Journal of Bone and Joint Surgery. British Volume. 2002 August; 84(6): 80711. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211669&dopt=Abstract
92
Chronic Pain
•
Management of chronic pain. Author(s): Howarth A. Source: Nurs Times. 2002 August 6-12; 98(32): 52-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211916&dopt=Abstract
•
Managing cancer and noncancer chronic pain in critical care settings. Knowledge and skills every nurse needs to know. Author(s): Curtiss CP, Haylock PJ. Source: Critical Care Nursing Clinics of North America. 2001 June; 13(2): 271-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866408&dopt=Abstract
•
Managing chronic pain in children and adolescents. We need to address the embarrassing lack of data for this common problem. Author(s): Eccleston C, Malleson P. Source: Bmj (Clinical Research Ed.). 2003 June 28; 326(7404): 1408-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829527&dopt=Abstract
•
Managing chronic pain in children and adolescents: effective responses are possible with non-evidence based clinical practice. Author(s): Dutton P. Source: Bmj (Clinical Research Ed.). 2003 September 20; 327(7416): 681. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500452&dopt=Abstract
•
Managing chronic pain in children and adolescents: procedural sedation should be considered. Author(s): Barbi E, Gerarduzzi T, Marchetti F. Source: Bmj (Clinical Research Ed.). 2003 September 20; 327(7416): 681. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500450&dopt=Abstract
•
Managing chronic pain in children and adolescents: tethered cord syndrome should be considered. Author(s): Giles LG. Source: Bmj (Clinical Research Ed.). 2003 September 20; 327(7416): 681. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500451&dopt=Abstract
•
Managing chronic pain in children. Author(s): Aitkenhead S. Source: Nurs Times. 2001 July 19-25; 97(29): 34-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11957502&dopt=Abstract
Studies
93
•
Managing chronic pain in the primary care setting. Author(s): Marcus DA. Source: American Family Physician. 2002 July 1; 66(1): 36, 38, 41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126033&dopt=Abstract
•
Managing chronic pain of spinal origin after lumbar surgery: the role of decompressive surgery. Author(s): Phillips FM, Cunningham B. Source: Spine. 2002 November 15; 27(22): 2547-53; Discussion 2554. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435991&dopt=Abstract
•
Manipulation and mobilization in the treatment of chronic pain. Author(s): Mior S. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S70-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783834&dopt=Abstract
•
Measuring counterdependency in patients with chronic pain. Author(s): Gregory RJ, Berry SL. Source: Psychosomatic Medicine. 1999 May-June; 61(3): 341-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367614&dopt=Abstract
•
Medical history and chronic pain. Author(s): Hunter J. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S20-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783827&dopt=Abstract
•
Medullary and CNS dysfunction in chronic pain. Author(s): Saberski LR. Source: The Clinical Journal of Pain. 1999 June; 15(2): 155. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382932&dopt=Abstract
•
Microelectrode findings in the thalamus in chronic pain and other conditions. Author(s): Tasker RR. Source: Stereotactic and Functional Neurosurgery. 2001; 77(1-4): 166-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378070&dopt=Abstract
•
MMPI-2 characteristics in a chronic pain population. Author(s): Slesinger D, Archer RP, Duane W. Source: Assessment. 2002 December; 9(4): 406-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462761&dopt=Abstract
94
Chronic Pain
•
Multimodal chronic pain rehabilitation program: its effect on immune function, depression, and health behaviors. Author(s): Vines SW, Ng AK, Breggia A, Mahoney R. Source: Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. 2000 September-October; 25(5): 185-91, 196. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11998084&dopt=Abstract
•
N of 1 randomised controlled trials of oral ketamine in patients with chronic pain. Author(s): Haines DR, Gaines SP. Source: Pain. 1999 November; 83(2): 283-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534600&dopt=Abstract
•
Negative affect, self-report of depressive symptoms, and clinical depression: relation to the experience of chronic pain. Author(s): Geisser ME, Roth RS, Theisen ME, Robinson ME, Riley JL 3rd. Source: The Clinical Journal of Pain. 2000 June; 16(2): 110-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870723&dopt=Abstract
•
Nerve blocks in chronic pain therapy--are there any indications left? Author(s): Stanton-Hicks M. Source: Acta Anaesthesiologica Scandinavica. 2001 October; 45(9): 1100-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683660&dopt=Abstract
•
Neuraxial medication delivery: the development and maturity of a concept for treating chronic pain of spinal origin. Author(s): Prager JP. Source: Spine. 2002 November 15; 27(22): 2593-605; Discussion 2606. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435999&dopt=Abstract
•
Neurocognitive performance and emotional status in chronic pain patients. Author(s): Iezzi T, Archibald Y, Barnett P, Klinck A, Duckworth M. Source: Journal of Behavioral Medicine. 1999 June; 22(3): 205-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10422614&dopt=Abstract
•
Neuroimaging of chronic pain: phantom limb and musculoskeletal pain. Author(s): Wiech K, Preissl H, Birbaumer N. Source: Scand J Rheumatol Suppl. 2000; 113: 13-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11028825&dopt=Abstract
Studies
95
•
Neurons with spontaneous high-frequency discharges in the central nervous system and chronic pain. Author(s): Yamashiro K, Tomiyama N, Terada Y, Samura H, Mukawa J, Tasker RR. Source: Acta Neurochir Suppl. 2003; 87: 153-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14518544&dopt=Abstract
•
Neuroplasticity--an important factor in acute and chronic pain. Author(s): Petersen-Felix S, Curatolo M. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 June 1; 132(21-22): 273-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362284&dopt=Abstract
•
No changes in mood with the seasons: observations in 3000 chronic pain patients. Author(s): Hardt J, Gerbershagen HU. Source: Acta Psychiatrica Scandinavica. 1999 October; 100(4): 288-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10510698&dopt=Abstract
•
Nonlocal and subtle energetic aspects of chronic pain. Author(s): Leskowitz E. Source: Alternative Therapies in Health and Medicine. 2001 September-October; 7(5): 144, 140-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11565393&dopt=Abstract
•
Nonopioid and adjuvant analgesics in chronic pain management: strategies for effective use. Author(s): Gordon DB. Source: Nurs Clin North Am. 2003 September; 38(3): 447-64, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567202&dopt=Abstract
•
Nurse-led pain management program: effect on self-efficacy, pain intensity, painrelated disability, and depressive symptoms in chronic pain patients. Author(s): Wells-Federman C, Arnstein P, Caudill M. Source: Pain Management Nursing : Official Journal of the American Society of Pain Management Nurses. 2002 December; 3(4): 131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454805&dopt=Abstract
•
Observation of a paradoxical temperature increase during cognitive stress in some chronic pain patients. Author(s): Wickramasekera IE, Kolm P, Pope A, Turner M. Source: Applied Psychophysiology and Biofeedback. 1998 December; 23(4): 233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457814&dopt=Abstract
96
Chronic Pain
•
Obtaining informed consent for cancer pain research: do patients with advanced cancer and patients with chronic pain have different concerns? Author(s): Casarett D, Karlawish J, Sankar P, Hirschman KB, Asch DA. Source: Journal of Pain and Symptom Management. 2002 November; 24(5): 506-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547050&dopt=Abstract
•
Older women's experiences with chronic pain: daily challenges and self-care practices. Author(s): Roberto KA, Reynolds SG. Source: J Women Aging. 2002; 14(3-4): 5-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537073&dopt=Abstract
•
Opiate candidacy and compliance in the treatment of chronic pain. Author(s): Chen J, Cole J, Staviski G. Source: J Miss State Med Assoc. 2002 May; 43(5): 139-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032987&dopt=Abstract
•
Opioid formulations: tailoring to the needs in chronic pain. Author(s): Reder RF. Source: European Journal of Pain (London, England). 2001; 5 Suppl A: 109-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798229&dopt=Abstract
•
Opioid therapy of chronic pain: assessment of consequences. Author(s): Savage SR. Source: Acta Anaesthesiologica Scandinavica. 1999 October; 43(9): 909-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10522738&dopt=Abstract
•
Opioid use in chronic pain management in the Philippines. Author(s): Javier FO, Magpantay LA, Espinosa EL, Harder SM, Unite MA. Source: European Journal of Pain (London, England). 2001; 5 Suppl A: 83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798224&dopt=Abstract
•
Opioid use in the management of chronic pain. Author(s): Savage SR. Source: The Medical Clinics of North America. 1999 May; 83(3): 761-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10386124&dopt=Abstract
•
Opioids and the treatment of chronic pain in a primary care sample. Author(s): Adams NJ, Plane MB, Fleming MF, Mundt MP, Saunders LA, Stauffacher EA. Source: Journal of Pain and Symptom Management. 2001 September; 22(3): 791-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532592&dopt=Abstract
Studies
97
•
Opioids in chronic non-malignant pain. Chronic pain should not be undertreated. Author(s): Lawhern RA. Source: Bmj (Clinical Research Ed.). 2001 September 8; 323(7312): 572. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573487&dopt=Abstract
•
Opioids in chronic non-malignant pain. Don't forget methadone for chronic pain. Author(s): Byrne A. Source: Bmj (Clinical Research Ed.). 2001 September 8; 323(7312): 572. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573488&dopt=Abstract
•
Opioids in chronic pain management: is there a significant risk of addiction? Author(s): Aronoff GM. Source: Current Review of Pain. 2000; 4(2): 112-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10998722&dopt=Abstract
•
Opioids in chronic pain. Author(s): Przewlocki R, Przewlocka B. Source: European Journal of Pharmacology. 2001 October 19; 429(1-3): 79-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11698029&dopt=Abstract
•
Orofacial pain: just another chronic pain? Results from a population-based survey. Author(s): Macfarlane TV, Blinkhorn AS, Davies RM, Ryan P, Worthington HV, Macfarlane GJ. Source: Pain. 2002 October; 99(3): 453-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406520&dopt=Abstract
•
Orthopaedic management of chronic pain: pain management for the cancer patient. Author(s): Nicholas RW, Thompson AR. Source: Instr Course Lect. 2000; 49: 513-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829205&dopt=Abstract
•
Outcome of patients with chronic abdominal pain referred to chronic pain clinic. Author(s): McGarrity TJ, Peters DJ, Thompson C, McGarrity SJ. Source: The American Journal of Gastroenterology. 2000 July; 95(7): 1812-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10925989&dopt=Abstract
•
Outcome of patients with severe chronic pain following repair of groin hernia. Author(s): Courtney CA, Duffy K, Serpell MG, O'Dwyer PJ. Source: The British Journal of Surgery. 2002 October; 89(10): 1310-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296903&dopt=Abstract
98
Chronic Pain
•
Pain anxiety among chronic pain patients: specific phobia or manifestation of anxiety sensitivity? Author(s): Greenberg J, Burns JW. Source: Behaviour Research and Therapy. 2003 February; 41(2): 223-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547382&dopt=Abstract
•
Pain perception across the menstrual cycle phases in women with chronic pain. Author(s): Hellstrom B, Anderberg UM. Source: Percept Mot Skills. 2003 February; 96(1): 201-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705527&dopt=Abstract
•
Pathophysiology of chronic pain disorders. Author(s): Teasell RW. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S8-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783836&dopt=Abstract
•
Patients with chronic pain and abnormal pituitary function require investigation. Author(s): Merza Z, Edwards N, Walters SJ, Newell-Price J, Ross RJ. Source: Lancet. 2003 June 28; 361(9376): 2203-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842375&dopt=Abstract
•
Pharmacokinetics and pharmacodynamics of intrathecal ziconotide in chronic pain patients. Author(s): Wermeling D, Drass M, Ellis D, Mayo M, McGuire D, O'Connell D, Hale V, Chao S. Source: Journal of Clinical Pharmacology. 2003 June; 43(6): 624-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817525&dopt=Abstract
•
Pharmacokinetics of an implanted osmotic pump delivering sufentanil for the treatment of chronic pain. Author(s): Fisher DM, Kellett N, Lenhardt R. Source: Anesthesiology. 2003 October; 99(4): 929-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508328&dopt=Abstract
•
Pharmacology of opioid and nonopioid analgesics in chronic pain states. Author(s): Martin TJ, Eisenach JC. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 December; 299(3): 811-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11714863&dopt=Abstract
Studies
99
•
Physical disability and the experience of chronic pain. Author(s): Dudgeon BJ, Gerrard BC, Jensen MP, Rhodes LA, Tyler EJ. Source: Archives of Physical Medicine and Rehabilitation. 2002 February; 83(2): 229-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833027&dopt=Abstract
•
Physical modalities in chronic pain management. Author(s): Rakel B, Barr JO. Source: Nurs Clin North Am. 2003 September; 38(3): 477-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567204&dopt=Abstract
•
Physical symptoms and signs and chronic pain. Author(s): Hunter J. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S26-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783828&dopt=Abstract
•
Physically unexplained chronic pain and its impact on children and their families: the mother's perception. Author(s): Hunfeld JA, Perquin CW, Hazebroek-Kampschreur AA, Passchier J, van Suijlekom-Smit LW, van der Wouden JC. Source: Psychology and Psychotherapy. 2002 September; 75(Pt 3): 251-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396752&dopt=Abstract
•
Presence of post-concussion syndrome symptoms in patients with chronic pain vs mild traumatic brain injury. Author(s): Smith-Seemiller L, Fow NR, Kant R, Franzen MD. Source: Brain Injury : [bi]. 2003 March; 17(3): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623496&dopt=Abstract
•
Prevalence and characteristics of chronic pain among chemically dependent patients in methadone maintenance and residential treatment facilities. Author(s): Rosenblum A, Joseph H, Fong C, Kipnis S, Cleland C, Portenoy RK. Source: Jama : the Journal of the American Medical Association. 2003 May 14; 289(18): 2370-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746360&dopt=Abstract
•
Prevention of chronic pain: the unexplored frontier. Author(s): Nielson WR, Mior S. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S68-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783833&dopt=Abstract
100 Chronic Pain
•
Psychological factors and the development of chronic pain. Author(s): Kuch K. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S33-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783829&dopt=Abstract
•
Psychological factors in chronic pain: evolution and revolution. Author(s): Turk DC, Okifuji A. Source: Journal of Consulting and Clinical Psychology. 2002 June; 70(3): 678-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090376&dopt=Abstract
•
Psychometric properties of the Pain Attitudes Questionnaire (revised) in adult patients with chronic pain. Author(s): Yong HH, Bell R, Workman B, Gibson SJ. Source: Pain. 2003 August; 104(3): 673-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927640&dopt=Abstract
•
Psychosocial factors associated with chronic pain in adolescents. Author(s): Merlijn VP, Hunfeld JA, van der Wouden JC, Hazebroek-Kampschreur AA, Koes BW, Passchier J. Source: Pain. 2003 January; 101(1-2): 33-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507698&dopt=Abstract
•
Psychosocial predictors of physical performance in disabled individuals with chronic pain. Author(s): Rudy TE, Lieber SJ, Boston JR, Gourley LM, Baysal E. Source: The Clinical Journal of Pain. 2003 January-February; 19(1): 18-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514453&dopt=Abstract
•
Psychosomatic concepts in chronic pain. Author(s): Rashbaum IG, Sarno JE. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S76-80; Quiz S81-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708562&dopt=Abstract
•
Qi therapy as an intervention to reduce chronic pain and to enhance mood in elderly subjects: a pilot study. Author(s): Lee MS, Yang KH, Huh HJ, Kim HW, Ryu H, Lee HS, Chung HT. Source: The American Journal of Chinese Medicine. 2001; 29(2): 237-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527067&dopt=Abstract
Studies
101
•
Quality of life in adolescents with chronic pain in the head or at other locations. Author(s): Hunfeld JA, Passchier J, Perquin CW, Hazebroek-Kampschreur AA, van Suijlekom-Smit LW, van der Wouden JC. Source: Cephalalgia : an International Journal of Headache. 2001 April; 21(3): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442555&dopt=Abstract
•
Quantitative analysis of nociceptin in blood of patients with acute and chronic pain. Author(s): Ko MH, Kim YH, Woo RS, Kim KW. Source: Neuroreport. 2002 September 16; 13(13): 1631-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352616&dopt=Abstract
•
Racial/ethnic differences in the experience of chronic pain. Author(s): Riley JL 3rd, Wade JB, Myers CD, Sheffield D, Papas RK, Price DD. Source: Pain. 2002 December; 100(3): 291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468000&dopt=Abstract
•
Radiofrequency ablation for chronic pain control. Author(s): Kapural L, Mekhail N. Source: Current Pain and Headache Reports. 2001 December; 5(6): 517-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11676886&dopt=Abstract
•
Radiofrequency lesions of the stellate ganglion in chronic pain syndromes: retrospective analysis of clinical efficacy in 86 patients. Author(s): Forouzanfar T, van Kleef M, Weber WE. Source: The Clinical Journal of Pain. 2000 June; 16(2): 164-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870729&dopt=Abstract
•
Radiofrequency procedures in chronic pain. Author(s): Lord SM, Bogduk N. Source: Best Pract Res Clin Anaesthesiol. 2002 December; 16(4): 597-617. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516894&dopt=Abstract
•
Re: Chronic pain: the next frontier for child maltreatment research (Kendall-Tackett, 2001). Author(s): Bass C. Source: Child Abuse & Neglect. 2001 September; 25(9): 1133-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700687&dopt=Abstract
102 Chronic Pain
•
Re: Management of cancer-related and non-cancer-related chronic pain in Connecticut: successes and failures. Author(s): Brennan MJ. Source: Conn Med. 2003 January; 67(1): 49-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630188&dopt=Abstract
•
Re: McCraken et al., A comparison of blacks and whites seeking treatment for chronic pain. Clin J Pain 2001;17:249-55. Author(s): Fillingim RB, Edwards RR, Doleys DM. Source: The Clinical Journal of Pain. 2002 March-April; 18(2): 136-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882779&dopt=Abstract
•
Readiness to adopt the self-management approach to cope with chronic pain in fibromyalgic patients. Author(s): Dijkstra A, Vlaeyen JW, Rijnen H, Nielson W. Source: Pain. 2001 February 1; 90(1-2): 37-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166968&dopt=Abstract
•
Readiness to self-manage pain is associated with coping and with psychological and physical functioning among patients with chronic pain. Author(s): Jensen MP, Nielson WR, Turner JA, Romano JM, Hill ML. Source: Pain. 2003 August; 104(3): 529-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927625&dopt=Abstract
•
Refractory chronic pain. Author(s): Clark MR, Cox TS. Source: The Psychiatric Clinics of North America. 2002 March; 25(1): 71-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912945&dopt=Abstract
•
Relationships among clinical characteristics of chronic pain after spinal cord injury. Author(s): Widerstrom-Noga EG, Felipe-Cuervo E, Yezierski RP. Source: Archives of Physical Medicine and Rehabilitation. 2001 September; 82(9): 1191-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552190&dopt=Abstract
•
Reliability, validity, and clinical utility of the research diagnostic criteria for Temporomandibular Disorders Axis II Scales: depression, non-specific physical symptoms, and graded chronic pain. Author(s): Dworkin SF, Sherman J, Mancl L, Ohrbach R, LeResche L, Truelove E. Source: J Orofac Pain. 2002; 16(3): 207-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221737&dopt=Abstract
Studies
103
•
Relief of chronic pain may be accompanied by an increase in a measure of heart rate variability. Author(s): Storella RJ, Shi Y, O'Connor DM, Pharo GH, Abrams JT, Levitt J. Source: Anesthesia and Analgesia. 1999 August; 89(2): 448-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439764&dopt=Abstract
•
Religious coping with chronic pain. Author(s): Bush EG, Rye MS, Brant CR, Emery E, Pargament KI, Riessinger CA. Source: Applied Psychophysiology and Biofeedback. 1999 December; 24(4): 249-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789001&dopt=Abstract
•
Repetitive transcranial magnetic stimulation for the treatment of chronic pain - a pilot study. Author(s): Rollnik JD, Wustefeld S, Dauper J, Karst M, Fink M, Kossev A, Dengler R. Source: European Neurology. 2002; 48(1): 6-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138303&dopt=Abstract
•
Repression predicts outcome following multidisciplinary treatment of chronic pain. Author(s): Burns JW. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 2000 January; 19(1): 75-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711590&dopt=Abstract
•
Responsible prescribing of opioids for the management of chronic pain. Author(s): Nicholson B. Source: Drugs. 2003; 63(1): 17-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487620&dopt=Abstract
•
Restoration of sensory function and lack of long-term chronic pain syndromes after brachial plexus injury in human neonates. Author(s): Anand P, Birch R. Source: Brain; a Journal of Neurology. 2002 January; 125(Pt 1): 113-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834597&dopt=Abstract
•
Role loss and emotional adjustment in chronic pain. Author(s): Harris S, Morley S, Barton SB. Source: Pain. 2003 September; 105(1-2): 363-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499455&dopt=Abstract
104 Chronic Pain
•
Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study. Author(s): Jaaskelainen SK, Rinne JO, Forssell H, Tenovuo O, Kaasinen V, Sonninen P, Bergman J. Source: Pain. 2001 February 15; 90(3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207397&dopt=Abstract
•
Satisfaction with treatment for chronic pain in a specialty service: preliminary prospective results. Author(s): McCracken LM, Evon D, Karapas ET. Source: European Journal of Pain (London, England). 2002; 6(5): 387-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160513&dopt=Abstract
•
Seasonal variation in effect of spa therapy on chronic pain. Author(s): Strauss-Blasche G, Ekmekcioglu C, Leibetseder V, Melchart H, Marktl W. Source: Chronobiology International. 2002 March; 19(2): 483-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025937&dopt=Abstract
•
Self-appraised problem solving and pain-relevant social support as predictors of the experience of chronic pain. Author(s): Kerns RD, Rosenberg R, Otis JD. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 2002 Spring; 24(2): 100-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054314&dopt=Abstract
•
Self-regulation training for chronic pain: can it be done effectively by telemedicine? Author(s): Appel PR, Bleiberg J, Noiseux J. Source: Telemedicine Journal and E-Health : the Official Journal of the American Telemedicine Association. 2002 Winter; 8(4): 361-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626105&dopt=Abstract
•
Sexual difficulties of chronic pain patients. Author(s): Ambler N, Williams AC, Hill P, Gunary R, Cratchley G. Source: The Clinical Journal of Pain. 2001 June; 17(2): 138-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444715&dopt=Abstract
•
Sexuality and chronic pain. Author(s): Paice J. Source: The American Journal of Nursing. 2003 January; 103(1): 87-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544064&dopt=Abstract
Studies
105
•
Shortening a quality of life questionnaire for adolescents with chronic pain and its psychometric qualities. Author(s): Merlijn VP, Hunfeld JA, van der Wouden JC, Hazebroek-Kampschreur AA, Passchier J. Source: Psychological Reports. 2002 June; 90(3 Pt 1): 753-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090503&dopt=Abstract
•
Should opioid analgesics be used in the management of chronic pain in opiate addicts? Author(s): Collins ED, Streltzer J. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2003 March-April; 12(2): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746085&dopt=Abstract
•
Sleep and chronic pain: challenges to the alpha-EEG sleep pattern as a pain specific sleep anomaly. Author(s): Rains JC, Penzien DB. Source: Journal of Psychosomatic Research. 2003 January; 54(1): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505558&dopt=Abstract
•
Sleep quality in chronic pain patients. Author(s): Sayar K, Arikan M, Yontem T. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 November; 47(9): 844-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500754&dopt=Abstract
•
Somatization and chronic pain. Author(s): Birket-Smith M. Source: Acta Anaesthesiologica Scandinavica. 2001 October; 45(9): 1114-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683662&dopt=Abstract
•
Spectroscopic brain mapping the N-acetyl aspartate to cognitive-perceptual states in chronic pain. Author(s): Grachev ID. Source: Molecular Psychiatry. 2001 March; 6(2): 124. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11317210&dopt=Abstract
•
Spinal cord stimulation for chronic pain of spinal origin: a valuable long-term solution. Author(s): North RB, Wetzel FT. Source: Spine. 2002 November 15; 27(22): 2584-91; Discussion 2592. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435997&dopt=Abstract
106 Chronic Pain
•
Spinal cord stimulation--a long-term evaluation in patients with chronic pain. Author(s): Kay AD, McIntyre MD, Macrae WA, Varma TR. Source: British Journal of Neurosurgery. 2001 August; 15(4): 335-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599450&dopt=Abstract
•
Spiritual healing as a therapy for chronic pain: a randomized, clinical trial. Author(s): Walach H, Lewith G, Bosch H, Utts J. Source: Pain. 2002 April; 96(3): 403-5; Author Reply 405-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973015&dopt=Abstract
•
Spiritual healing as a therapy for chronic pain: a randomized, clinical trial. Author(s): Abbot NC, Harkness EF, Stevinson C, Marshall FP, Conn DA, Ernst E. Source: Pain. 2001 March; 91(1-2): 79-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11240080&dopt=Abstract
•
Spousal responses are differentially associated with clinical variables in women and men with chronic pain. Author(s): Fillingim RB, Doleys DM, Edwards RR, Lowery D. Source: The Clinical Journal of Pain. 2003 July-August; 19(4): 217-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840615&dopt=Abstract
•
State Medical Society of Wisconsin statement on the use of opioids for the treatment of chronic pain. Author(s): American Academy of Pain Medicine and the American Pain Society. Source: Wmj. 2001; 100(5): 22-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11579795&dopt=Abstract
•
Suicidal intent in patients with chronic pain. Author(s): Fisher BJ, Haythornthwaite JA, Heinberg LJ, Clark M, Reed J. Source: Pain. 2001 January; 89(2-3): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166476&dopt=Abstract
•
Sympathetic blockade for the relief of chronic pain. Author(s): Chaturvedi A, Dash HH. Source: J Indian Med Assoc. 2001 December; 99(12): 698-703. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022220&dopt=Abstract
•
Testing a theory of chronic pain. Author(s): Tsai PF, Tak S, Moore C, Palencia I. Source: Journal of Advanced Nursing. 2003 July; 43(2): 158-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834374&dopt=Abstract
Studies
107
•
The Chronic Pain Coping Inventory-42: reliability and validity. Author(s): Romano JM, Jensen MP, Turner JA. Source: Pain. 2003 July; 104(1-2): 65-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855315&dopt=Abstract
•
The cognitive specificity of associative responses in patients with chronic pain. Author(s): McKellar JD, Clark ME, Shriner J. Source: The British Journal of Clinical Psychology / the British Psychological Society. 2003 March; 42(Pt 1): 27-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675977&dopt=Abstract
•
The disruptive effect of chronic pain on mismatch negativity. Author(s): Dick BD, Connolly JF, McGrath PJ, Finley GA, Stroink G, Houlihan ME, Clark AJ. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 August; 114(8): 1497-506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888033&dopt=Abstract
•
The pain vigilance and awareness questionnaire (PVAQ): further psychometric evaluation in fibromyalgia and other chronic pain syndromes. Author(s): Roelofs J, Peters ML, McCracken L, Vlaeyen JW. Source: Pain. 2003 February; 101(3): 299-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583873&dopt=Abstract
•
The relationship between chronic pain, immune function, depression, and health behaviors. Author(s): Vines SW, Gupta S, Whiteside T, Dostal-Johnson D, Hummler-Davis A. Source: Biological Research for Nursing. 2003 July; 5(1): 18-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886667&dopt=Abstract
•
The relationship of attachment style to depression, catastrophizing and health care utilization in patients with chronic pain. Author(s): Ciechanowski P, Sullivan M, Jensen M, Romano J, Summers H. Source: Pain. 2003 August; 104(3): 627-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927635&dopt=Abstract
•
The relevance of health anxiety to chronic pain: research findings and recommendations for assessment and treatment. Author(s): Hadjistavropoulos HD, Hadjistavropoulos T. Source: Current Pain and Headache Reports. 2003 April; 7(2): 98-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628051&dopt=Abstract
108 Chronic Pain
•
The role of childhood and adulthood abuse among women presenting for chronic pain management. Author(s): Green CR, Flowe-Valencia H, Rosenblum L, Tait AR. Source: The Clinical Journal of Pain. 2001 December; 17(4): 359-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783817&dopt=Abstract
•
The role of operant conditioning in chronic pain: an experimental investigation. Author(s): Flor H, Knost B, Birbaumer N. Source: Pain. 2002 January; 95(1-2): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790473&dopt=Abstract
•
The role of spinal cholecystokinin in chronic pain states. Author(s): Wiesenfeld-Hallin Z, Xu XJ, Hokfelt T. Source: Pharmacology & Toxicology. 2002 December; 91(6): 398-403. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688385&dopt=Abstract
•
The short-term effects of fasting on the neuroendocrine system in patients with chronic pain syndromes. Author(s): Michalsen A, Schneider S, Rodenbeck A, Ludtke R, Huether G, Dobos GJ. Source: Nutritional Neuroscience. 2003 February; 6(1): 11-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608732&dopt=Abstract
•
The use of long-acting opioids in chronic pain management. Author(s): Vallerand AH. Source: Nurs Clin North Am. 2003 September; 38(3): 435-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567201&dopt=Abstract
•
Tips for managing chronic pain in the workplace. Author(s): Sitzman K. Source: Aaohn Journal : Official Journal of the American Association of Occupational Health Nurses. 2003 June; 51(6): 276. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846461&dopt=Abstract
•
Tips for managing chronic pain. Implementing the latest guidelines. Author(s): Marcus DA. Source: Postgraduate Medicine. 2003 April; 113(4): 49-50, 55-6, 59-60 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718235&dopt=Abstract
•
Transitions in the concept of chronic pain. Author(s): Breen J. Source: Ans. Advances in Nursing Science. 2002 June; 24(4): 48-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699276&dopt=Abstract
Studies
109
•
Trauma, chronic pain commonly underrated. Author(s): Kahler SC. Source: J Am Vet Med Assoc. 2001 December 15; 219(12): 1662, 1669. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767904&dopt=Abstract
•
Treatment of chronic pain in osteoarthritis: do opioids have a clinical role? Author(s): Lipman AG. Source: Curr Rheumatol Rep. 2001 December; 3(6): 513-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709114&dopt=Abstract
•
Treatment of chronic pain with millimetre wave therapy (MWT) in patients with diffuse connective tissue diseases: a pilot case series study. Author(s): Usichenko TI, Herget HF. Source: European Journal of Pain (London, England). 2003; 7(3): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725852&dopt=Abstract
•
Treatment of chronic pain. Author(s): Kernich CA. Source: The Neurologist. 2003 July; 9(4): 220-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864933&dopt=Abstract
•
Unexplained severe chronic pain in general practice. Author(s): Kerssens JJ, Verhaak PF, Bartelds AI, Sorbi MJ, Bensing JM. Source: European Journal of Pain (London, England). 2002; 6(3): 203-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036307&dopt=Abstract
•
Use of aromatherapy as a complementary treatment for chronic pain. Author(s): Buckle J. Source: Alternative Therapies in Health and Medicine. 1999 September; 5(5): 42-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10484830&dopt=Abstract
•
Using biologic markers to identify legitimate chronic pain. Author(s): Tennant F, Hermann L. Source: Am Clin Lab. 2002 June; 21(5): 14-5, 18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122778&dopt=Abstract
•
Using chronic pain to predict depressive morbidity in the general population. Author(s): Ohayon MM, Schatzberg AF. Source: Archives of General Psychiatry. 2003 January; 60(1): 39-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511171&dopt=Abstract
110 Chronic Pain
•
Using nominal group technique to assess chronic pain, patients' perceived challenges and needs in a community health region. Author(s): Dewar A, White M, Posade ST, Dillon W. Source: Health Expectations : an International Journal of Public Participation in Health Care and Health Policy. 2003 March; 6(1): 44-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603627&dopt=Abstract
•
Using outcome evaluations to assess interdisciplinary acute and chronic pain programs. Author(s): Hadjistavropoulos HD, Clark J. Source: Jt Comm J Qual Improv. 2001 July; 27(7): 335-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11433625&dopt=Abstract
•
Utilisation of health care system by chronic pain patients who applied for disability pensions. Author(s): Hojsted J, Alban A, Hagild K, Eriksen J. Source: Pain. 1999 September; 82(3): 275-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10488678&dopt=Abstract
•
Utilization of essential medications by vulnerable older people after a drug benefit cap: importance of mental disorders, chronic pain, and practice setting. Author(s): Fortess EE, Soumerai SB, McLaughlin TJ, Ross-Degnan D. Source: Journal of the American Geriatrics Society. 2001 June; 49(6): 793-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454120&dopt=Abstract
•
Validation of the WHOQOL-100: pain management improves quality of life for chronic pain patients. Author(s): Skevington SM, Carse MS, Williams AC. Source: The Clinical Journal of Pain. 2001 September; 17(3): 264-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587119&dopt=Abstract
•
Validity of self-reported drug use in chronic pain patients. Author(s): Fishbain DA, Cutler RB, Rosomoff HL, Rosomoff RS. Source: The Clinical Journal of Pain. 1999 September; 15(3): 184-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10524471&dopt=Abstract
•
Vicissitudes of pain and suffering: chronic pain and liminality. Author(s): Honkasalo ML. Source: Medical Anthropology. 2001; 19(4): 319-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800318&dopt=Abstract
Studies
111
•
Vulnerability to stress among women in chronic pain from fibromyalgia and osteoarthritis. Author(s): Davis MC, Zautra AJ, Reich JW. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 2001 Summer; 23(3): 215-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495222&dopt=Abstract
•
Vulvodynia: an introduction and critical review of a chronic pain condition. Author(s): Masheb RM, Nash JM, Brondolo E, Kerns RD. Source: Pain. 2000 May; 86(1-2): 3-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10779654&dopt=Abstract
•
Weather change and pain: a behavioral animal study of the influences of simulated meteorological changes on chronic pain. Author(s): Sato J. Source: International Journal of Biometeorology. 2003 March; 47(2): 55-61. Epub 2003 January 30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647091&dopt=Abstract
•
What is the most effective approach to chronic pain? Author(s): Gillette RD. Source: American Family Physician. 2003 February 1; 67(3): 473. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588070&dopt=Abstract
•
What is the quality of the implemented meta-analytic procedures in chronic pain treatment meta-analyses? Author(s): Fishbain D, Cutler RB, Rosomoff HL, Rosomoff RS. Source: The Clinical Journal of Pain. 2000 March; 16(1): 73-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741821&dopt=Abstract
•
What is the role of psychiatry in the management of chronic pain? Author(s): Mufson MJ. Source: The Harvard Mental Health Letter / from Harvard Medical School. 1999 September; 16(3): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10445985&dopt=Abstract
•
When there is no benchmark: designing a primary care-based chronic pain management program from the scientific basis up. Author(s): Donovan MI, Evers K, Jacobs P, Mandleblatt S. Source: Journal of Pain and Symptom Management. 1999 July; 18(1): 38-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439571&dopt=Abstract
112 Chronic Pain
•
Why is chronic pain so difficult to treat? Psychological considerations from simple to complex care. Author(s): Weisberg MB, Clavel AL Jr. Source: Postgraduate Medicine. 1999 November; 106(6): 141-2, 145-8, 157-60; Passim. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10576008&dopt=Abstract
•
Work-related beliefs about injury and physical capability for work in individuals with chronic pain. Author(s): Vowles KE, Gross RT. Source: Pain. 2003 February; 101(3): 291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583872&dopt=Abstract
•
Worry and chronic pain patients: a description and analysis of individual differences. Author(s): Eccleston C, Crombez G, Aldrich S, Stannard C. Source: European Journal of Pain (London, England). 2001; 5(3): 309-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558986&dopt=Abstract
113
CHAPTER 2. NUTRITION AND CHRONIC PAIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and chronic pain.
Finding Nutrition Studies on Chronic Pain The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “chronic pain” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
114 Chronic Pain
The following information is typical of that found when using the “Full IBIDS Database” to search for “chronic pain” (or a synonym): •
Analgesics in the management of chronic pain. Part four: Step 3 oral analgesic drug therapy. Source: MacConnachie, A M Intensive-Crit-Care-Nurs. 1998 December; 14(6): 318-9 0964-3397
•
Attack chronic pain to reduce ER visits, hospitalizations. Source: Anonymous Healthc-Demand-Dis-Manag. 1999 November; 5(11): 161-6 10942521
•
Cannabis for chronic pain: case series and implications for clinicians. Author(s): McGill University Health Centre-Montreal General Hospital Pain Centre, Montreal, Canada.
[email protected] Source: Ware, M A Gamsa, A Persson, J Fitzcharles, M A Pain-Res-Manag. 2002 Summer; 7(2): 95-9 1203-6765
•
Care of the patient with chronic pain: part II. Author(s): Dartmouth Hitchcock Clinic, Manchester, New Hampshire, USA.
[email protected] Source: Wells Federman C, L Clin-Excell-Nurse-Pract. 2000 January; 4(1): 4-12 1085-2360
•
Decreased levels of N-acetylaspartate in dorsolateral prefrontal cortex in a case of intractable severe sympathetically mediated chronic pain (complex regional pain syndrome, type I). Author(s): Department of Radiology, State University of New York Upstate Medical University, Syracuse 13210, USA.
[email protected] Source: Grachev, Igor D Thomas, P Sebastian Ramachandran, Tarakad S Brain-Cogn. 2002 June; 49(1): 102-13 0278-2626
•
Evaluating the use of Snoezelen and chronic pain: the findings of an investigation into its use (Part II). Author(s): University of Sheffield, Department of Nursing Studies, UK. Source: Schofield, P Davies, B Hutchinson, R Complement-Ther-Nurs-Midwifery. 1998 October; 4(5): 137-43 1353-6117
•
Gait analysis as an objective measure in a chronic pain model. Author(s): University Dental Hospital of Manchester, Higher Cambridge Street, Manchester, M15 6FH, UK.
[email protected] Source: Coulthard, Paul Pleuvry, Barbara J Brewster, Mike Wilson, Kevin L Macfarlane, Tatiana V J-Neurosci-Methods. 2002 May 15; 116(2): 197-213 0165-0270
•
Hydromorphone for acute and chronic pain. Author(s): Medical Oncology, Hammersmith Hospitals Trust, Du Cane Road, London, UK, W12 0NN.
[email protected] Source: Quigley, C Cochrane-Database-Syst-Revolume 2002; (1): CD003447 1469-493X
•
Intrathecal therapy for chronic pain. Author(s): Pain Relief Foundation, University of Liverpool, UK. Source: Miles, J Stereotact-Funct-Neurosurg. 2001; 77(1-4): 156-8 1011-6125
•
Opioid formulations: tailoring to the needs in chronic pain. Author(s): Purdue Pharma L.P., Stamford, Connecticut 06901-3431, USA. Source: Reder, R F Eur-J-Pain. 2001; 5 Suppl A: 109-11 1090-3801
Nutrition
115
•
Opioid use in chronic pain management in the Philippines. Author(s): Pain Management Center, St. Luke's Medical Center, Metro Manila, Philippines. Source: Javier, F O Magpantay, L A Espinosa, E L Harder, S M Unite, M A Eur-J-Pain. 2001; 5 Suppl A: 83-5 1090-3801
•
Preliminary study of chronic pain patients' concerns about cannabinoids as analgesics. Author(s): Division of Behavioural Medicine, Guy's King's & St. Thomas' School of Medicine, Biomedical Sciences and Dentistry, Guy's Hospital, London, United Kingdom. Source: Gill, A Williams, A C Clin-J-Pain. 2001 September; 17(3): 245-8 0749-8047
•
Qi therapy as an intervention to reduce chronic pain and to enhance mood in elderly subjects: a pilot study. Author(s): Department of Qi-Medicine, Institute of Biotechnology, Wonkwang University, Iksan, Republic of Korea. Source: Lee, M S Yang, K H Huh, H J Kim, H W Ryu, H Lee, H S Chung, H T Am-JChin-Med. 2001; 29(2): 237-45 0192-415X
•
Solving the puzzle of chronic pain. Author(s): Bay Life Partial Hospitalization Program, Baltimore, MD, USA. Source: Martin, S Nurs-Spectr-(Wash-D-C). 1998 June 15; 8(12): 17, 24 1098-9153
•
The use of complementary and alternative therapies for chronic pain following spinal cord injury: a pilot survey. Author(s): Department of Psychiatry, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07107, USA.
[email protected] Source: Nayak, S Matheis, R J Agostinelli, S Shifleft, S C J-Spinal-Cord-Med. 2001 Spring; 24(1): 54-62 1079-0268
•
Treatment of chronic pain by using intrathecal drug therapy compared with conventional pain therapies: a cost-effectiveness analysis. Author(s): Department of Surgery, Section of Neurosurgery, Regina General Hospital, University of Saskatchewan, Regina, Saskatchewan, Canada.
[email protected] Source: KuMarch, K Hunter, G Demeria, D D J-Neurosurg. 2002 October; 97(4): 803-10 0022-3085
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
•
The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
•
The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
•
The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
116 Chronic Pain
•
The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
•
Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
•
Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
•
Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
•
Google: http://directory.google.com/Top/Health/Nutrition/
•
Healthnotes: http://www.healthnotes.com/
•
Open Directory Project: http://dmoz.org/Health/Nutrition/
•
Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
•
WebMD®Health: http://my.webmd.com/nutrition
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to chronic pain; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Minerals Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html
•
Food and Diet Diabetes Source: Healthnotes, Inc.; www.healthnotes.com
117
CHAPTER 3. ALTERNATIVE MEDICINE AND CHRONIC PAIN Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to chronic pain. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “chronic pain” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Why Patients Use Alternative Medicine: Results of a National Study Source: JAMA. Journal of the American Medical Association. 279(19): 1548-1553. May 20, 1998. Summary: This journal article describes a national study of the reasons why patients use alternative medicine. The researchers focused on three theories: (1) patients are dissatisfied in some way with conventional medicine; (2) they believe alternative treatments offer more personal autonomy and control over health care decisions; and (3) they consider alternative therapies to be more compatible with their values, worldview, or beliefs about the nature and meaning of health and illness. Demographic variables and health status also were examined as possible predictors of alternative medicine use. A total of 1,035 individuals randomly selected from a national panel who had agreed to participate in mail surveys completed a written survey. The use of alternative health care was associated with more education, poorer health status, a holistic orientation to health, having had a transformational experience that changed the person's worldview,
118 Chronic Pain
and classification in a cultural group identifiable by a commitment to environmentalism, commitment to feminism, and interest in spirituality and personal growth psychology. Alternative medicine use also was predicted by the presence of anxiety, back problems, chronic pain, and/or urinary tract problems. Dissatisfaction with conventional medicine did not predict use of alternative medicine. Only 4.4 percent of respondents reported relying primarily on alternative therapies. The article has 5 tables and 34 references. •
Psychosocial Aspects of Complementary and Alternative Medicine Source: Pharmacotherapy. 20(11): 1289-1294. November 11, 2000. Summary: This journal article reviews patterns of complementary and alternative medicine (CAM) use in the United States. Between 1990 and 1997, the proportion of consumers using CAM increased from 33.8 percent to 42.1 percent. Among users, 46.3 percent saw a CAM practitioner and 53.7 percent used CAM on their own. CAM users tend to have high incomes and high levels of education. They are likely to have medical conditions such as chronic pain, poor mental health, human immunodeficiency virus infection, and cancer that are not easily treated by conventional medicine. Many of the most commonly used therapies are noninvasive, but dietary supplements also have become popular. Some therapies such as lifestyle modification, behavior modification, and relaxation techniques are routine parts of treatment plans. Others, such as acupuncture, chiropractic, and massage, are gaining acceptance from the medical community. Only 38.5 percent of CAM users reported this use to their physicians, often because they anticipated disinterest or disapproval from the doctor. More recent data suggest that physicians are more open to discussing CAM than patients perceive. With growing evidence of potential herb-drug interactions, the authors suggest that discussing CAM with patients is becoming even more important. The article has 2 figures and 24 references.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to chronic pain and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “chronic pain” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to chronic pain: •
A brief introductory guide to chronic pain resources on the Internet. Author(s): Martelli MF, Liljedahl EL, Nicholson K, Zasler ND. Source: Neurorehabilitation. 2000; 14(2): 105-121. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11455073&dopt=Abstract
•
A national study of the effect of chronic pain on the use of health care by depressed persons. Author(s): Bao Y, Sturm R, Croghan TW.
Alternative Medicine 119
Source: Psychiatric Services (Washington, D.C.). 2003 May; 54(5): 693-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719500&dopt=Abstract •
Acupuncture, transcutaneous electrical nerve stimulation, and laser therapy in chronic pain. Author(s): Fargas-Babjak A. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S105-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783823&dopt=Abstract
•
Are relaxation techniques effective in relief of chronic pain? Author(s): Lecky C. Source: Work (Reading, Mass.). 1999; 13(3): 249-256. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441550&dopt=Abstract
•
Assessment and management of chronic pain in elderly people. Author(s): Mitchell C. Source: British Journal of Nursing (Mark Allen Publishing). 2001 March 8-21; 10(5): 296304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170672&dopt=Abstract
•
Biopsychosocial approaches to the treatment of chronic pain. Author(s): Nielson WR, Weir R. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S114-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783824&dopt=Abstract
•
Building bridges between body and mind: The analysis of an adolescent with paralyzing chronic pain. Author(s): Shapiro B. Source: The International Journal of Psycho-Analysis. 2003 June; 84(Pt 3): 547-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873360&dopt=Abstract
•
Cannabis for chronic pain: case series and implications for clinicians. Author(s): Ware MA, Gamsa A, Persson J, Fitzcharles MA. Source: Pain Res Manag. 2002 Summer; 7(2): 95-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185373&dopt=Abstract
•
Care of the patient with chronic pain: part II. Author(s): Wells-Federman CL. Source: Clin Excell Nurse Pract. 2000 January; 4(1): 4-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858295&dopt=Abstract
120 Chronic Pain
•
Chronic pain and its management in primary care. Author(s): Smith L. Source: Southern Medical Journal. 2002 January; 95(1): 108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827242&dopt=Abstract
•
Chronic pain and the use of conventional and alternative therapy. Author(s): Haetzman M, Elliott AM, Smith BH, Hannaford P, Chambers WA. Source: Family Practice. 2003 April; 20(2): 147-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651788&dopt=Abstract
•
Chronic pain therapy: an evolution from solo-interventions to a holistic interdisciplinary patient approach. Author(s): Poppe C, Devulder J, Mariman A, Mortier E. Source: Acta Clin Belg. 2003 March-April; 58(2): 92-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836491&dopt=Abstract
•
Chronic pain with beneficial response to electroconvulsive therapy and regional cerebral blood flow changes assessed by single photon emission computed tomography. Author(s): Fukui S, Shigemori S, Yoshimura A, Nosaka S. Source: Regional Anesthesia and Pain Medicine. 2002 March-April; 27(2): 211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915071&dopt=Abstract
•
Chronic pain/dysfunction in whiplash-associated disorders. Author(s): Ferrari R. Source: Journal of Manipulative and Physiological Therapeutics. 2002 February; 25(2): 135; Author Reply 135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896383&dopt=Abstract
•
Chronic pain: psychological approaches for the front-line clinician. Author(s): Arena JG. Source: Journal of Clinical Psychology. 2002 November; 58(11): 1385-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412149&dopt=Abstract
•
Complementary and alternative therapies: what is their place in the management of chronic pain? Author(s): Snyder M, Wieland J. Source: Nurs Clin North Am. 2003 September; 38(3): 495-508. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567205&dopt=Abstract
•
Comprehensive analysis and management of chronic pain. Author(s): Arnstein P.
Alternative Medicine 121
Source: Nurs Clin North Am. 2003 September; 38(3): 403-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567199&dopt=Abstract •
Contribution of individual spa therapies in the treatment of chronic pain. Author(s): Strauss-Blasche G, Ekmekcioglu C, Vacariu G, Melchart H, Fialka-Moser V, Marktl W. Source: The Clinical Journal of Pain. 2002 September-October; 18(5): 302-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218501&dopt=Abstract
•
Differential relationships between anxiety and treatment-associated pain reduction among male and female chronic pain patients. Author(s): Edwards R, Augustson E, Fillingim R. Source: The Clinical Journal of Pain. 2003 July-August; 19(4): 208-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840614&dopt=Abstract
•
Does pain relief improve pain behavior and mood in chronic pain patients? Author(s): Sator-Katzenschlager SM, Schiesser AW, Kozek-Langenecker SA, Benetka G, Langer G, Kress HG. Source: Anesthesia and Analgesia. 2003 September; 97(3): 791-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933404&dopt=Abstract
•
EMDR in the treatment of chronic pain. Author(s): Grant M, Threlfo C. Source: Journal of Clinical Psychology. 2002 December; 58(12): 1505-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455018&dopt=Abstract
•
Evaluating Snoezelen for relaxation within chronic pain management. Author(s): Schofield P. Source: British Journal of Nursing (Mark Allen Publishing). 2002 June 27-July 10; 11(12): 812-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131831&dopt=Abstract
•
Ezzo et al.: Is acupuncture effective for the treatment of chronic pain? A systematic review, PAIN 86(2000)217-225. Author(s): Mendelson G. Source: Pain. 2001 August; 93(2): 198-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486756&dopt=Abstract
•
Health status of patients with chronic pain attending a pain center. Author(s): Wilkes LM, Castro M, Mohan S, Sundaraj SR, Noore F.
122 Chronic Pain
Source: Pain Management Nursing : Official Journal of the American Society of Pain Management Nurses. 2003 June; 4(2): 70-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836151&dopt=Abstract •
How can we learn to live with pain? A Q-methodological analysis of the diverse understandings of acceptance of chronic pain. Author(s): Risdon A, Eccleston C, Crombez G, McCracken L. Source: Social Science & Medicine (1982). 2003 January; 56(2): 375-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473322&dopt=Abstract
•
Interventions in chronic pain management. 2. New frontiers: invasive nonsurgical interventions. Author(s): Shah RV, Ericksen JJ, Lacerte M. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S39-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708557&dopt=Abstract
•
Interventions in chronic pain management. 3. New frontiers in pain management: complementary techniques. Author(s): Braverman DL, Ericken JJ, Shah RV, Franklin DJ. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S45-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708558&dopt=Abstract
•
Interventions in chronic pain management. 4. Medications in pain management. Author(s): Ericksen JJ, Braverman DL, Shah RV. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S50-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708559&dopt=Abstract
•
Is acupuncture effective in treating chronic pain after spinal cord injury? Author(s): Nayak S, Shiflett SC, Schoenberger NE, Agostinelli S, Kirshblum S, Averill A, Cotter AC. Source: Archives of Physical Medicine and Rehabilitation. 2001 November; 82(11): 157886. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689979&dopt=Abstract
•
Linking chronic pain and depression. Author(s): Gray E. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2001 March 7-13; 15(25): 33-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211823&dopt=Abstract
Alternative Medicine 123
•
Manipulation and mobilization in the treatment of chronic pain. Author(s): Mior S. Source: The Clinical Journal of Pain. 2001 December; 17(4 Suppl): S70-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783834&dopt=Abstract
•
Molecular plasticity of primary nociceptive neurons: relations of the NGF-c-jun system to neurotomy and chronic pain. Author(s): Csillik B, Janka Z, Boncz I, Kalman J, Mihaly A, Vecsei L, Knyihar E. Source: Ann Anat. 2003 July; 185(4): 303-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924468&dopt=Abstract
•
Nonlocal and subtle energetic aspects of chronic pain. Author(s): Leskowitz E. Source: Alternative Therapies in Health and Medicine. 2001 September-October; 7(5): 144, 140-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11565393&dopt=Abstract
•
Patient satisfaction with chronic pain management. Author(s): McHugh G, Thoms G. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2001 September 5-11; 15(51): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206059&dopt=Abstract
•
Physical modalities in chronic pain management. Author(s): Rakel B, Barr JO. Source: Nurs Clin North Am. 2003 September; 38(3): 477-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567204&dopt=Abstract
•
Psychosomatic concepts in chronic pain. Author(s): Rashbaum IG, Sarno JE. Source: Archives of Physical Medicine and Rehabilitation. 2003 March; 84(3 Suppl 1): S76-80; Quiz S81-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708562&dopt=Abstract
•
Qi therapy as an intervention to reduce chronic pain and to enhance mood in elderly subjects: a pilot study. Author(s): Lee MS, Yang KH, Huh HJ, Kim HW, Ryu H, Lee HS, Chung HT. Source: The American Journal of Chinese Medicine. 2001; 29(2): 237-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527067&dopt=Abstract
•
Repetitive transcranial magnetic stimulation for the treatment of chronic pain - a pilot study. Author(s): Rollnik JD, Wustefeld S, Dauper J, Karst M, Fink M, Kossev A, Dengler R.
124 Chronic Pain
Source: European Neurology. 2002; 48(1): 6-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138303&dopt=Abstract •
Seasonal variation in effect of spa therapy on chronic pain. Author(s): Strauss-Blasche G, Ekmekcioglu C, Leibetseder V, Melchart H, Marktl W. Source: Chronobiology International. 2002 March; 19(2): 483-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025937&dopt=Abstract
•
Spiritual healing as a therapy for chronic pain: a randomized, clinical trial. Author(s): Walach H, Lewith G, Bosch H, Utts J. Source: Pain. 2002 April; 96(3): 403-5; Author Reply 405-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973015&dopt=Abstract
•
Spiritual healing as a therapy of chronic pain: a randomized, clinical trial. Author(s): Everett W, Aberra F, Bisson G, Casanova B, Pare E, Piasecki B. Source: Pain. 2002 March; 96(1-2): 219-20; Author Reply 220. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932081&dopt=Abstract
•
The assessment and management of chronic pain in children. Author(s): Chambliss CR, Heggen J, Copelan DN, Pettignano R. Source: Paediatric Drugs. 2002; 4(11): 737-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390045&dopt=Abstract
•
The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases? Author(s): Seaman DR. Source: Journal of Manipulative and Physiological Therapeutics. 2002 March-April; 25(3): 168-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986578&dopt=Abstract
•
The disruptive effect of chronic pain on mismatch negativity. Author(s): Dick BD, Connolly JF, McGrath PJ, Finley GA, Stroink G, Houlihan ME, Clark AJ. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 August; 114(8): 1497-506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888033&dopt=Abstract
•
The effects of Snoezelen on chronic pain. Author(s): Schofield P.
Alternative Medicine 125
Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2000 September 20-26; 15(1): 33-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971385&dopt=Abstract •
The heterogeneous pain personality: diverse coping styles among sufferers of chronic pain. Author(s): Cipher DJ, Clifford PA, Schumacker RE. Source: Alternative Therapies in Health and Medicine. 2002 November-December; 8(6): 60-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440840&dopt=Abstract
•
The modification of cortical reorganization and chronic pain by sensory feedback. Author(s): Flor H. Source: Applied Psychophysiology and Biofeedback. 2002 September; 27(3): 215-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206052&dopt=Abstract
•
The short-term effects of fasting on the neuroendocrine system in patients with chronic pain syndromes. Author(s): Michalsen A, Schneider S, Rodenbeck A, Ludtke R, Huether G, Dobos GJ. Source: Nutritional Neuroscience. 2003 February; 6(1): 11-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608732&dopt=Abstract
•
The use of complementary and alternative therapies for chronic pain following spinal cord injury: a pilot survey. Author(s): Nayak S, Matheis RJ, Agostinelli S, Shifleft SC. Source: J Spinal Cord Med. 2001 Spring; 24(1): 54-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587436&dopt=Abstract
•
The use of cranial electrotherapy stimulation in the management of chronic pain: A review. Author(s): Kirsch DL, Smith RB. Source: Neurorehabilitation. 2000; 14(2): 85-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11455071&dopt=Abstract
•
Transcutaneous electrical nerve stimulation (TENS) for chronic pain. Author(s): Carroll D, Moore RA, McQuay HJ, Fairman F, Tramer M, Leijon G. Source: Cochrane Database Syst Rev. 2001; (3): Cd003222. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687055&dopt=Abstract
•
Treatment of chronic pain by using intrathecal drug therapy compared with conventional pain therapies: a cost-effectiveness analysis. Author(s): Kumar K, Hunter G, Demeria DD.
126 Chronic Pain
Source: Journal of Neurosurgery. 2002 October; 97(4): 803-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405366&dopt=Abstract •
Treatment of chronic pain with spinal cord stimulation versus alternative therapies: cost-effectiveness analysis. Author(s): Kumar K, Malik S, Demeria D. Source: Neurosurgery. 2002 July; 51(1): 106-15; Discussion 115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182407&dopt=Abstract
•
Treatment of chronic pain. Author(s): Kernich CA. Source: The Neurologist. 2003 July; 9(4): 220-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864933&dopt=Abstract
•
Treatments for chronic pain associated with spinal cord injuries: many are tried, few are helpful. Author(s): Warms CA, Turner JA, Marshall HM, Cardenas DD. Source: The Clinical Journal of Pain. 2002 May-June; 18(3): 154-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048417&dopt=Abstract
•
Types and effectiveness of treatments used by people with chronic pain associated with spinal cord injuries: influence of pain and psychosocial characteristics. Author(s): Widerstrom-Noga EG, Turk DC. Source: Spinal Cord : the Official Journal of the International Medical Society of Paraplegia. 2003 November; 41(11): 600-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14569261&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
•
AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
•
Chinese Medicine: http://www.newcenturynutrition.com/
•
drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
•
Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
•
Google: http://directory.google.com/Top/Health/Alternative/
•
Healthnotes: http://www.healthnotes.com/
•
MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
Alternative Medicine 127
•
Open Directory Project: http://dmoz.org/Health/Alternative/
•
HealthGate: http://www.tnp.com/
•
WebMD®Health: http://my.webmd.com/drugs_and_herbs
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
•
Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to chronic pain; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Depression Source: Integrative Medicine Communications; www.drkoop.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Low Back Pain Source: Healthnotes, Inc.; www.healthnotes.com Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com Nausea Source: Prima Communications, Inc.www.personalhealthzone.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Pain Source: Healthnotes, Inc.; www.healthnotes.com Prostatitis Source: Healthnotes, Inc.; www.healthnotes.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com
128 Chronic Pain
Vertigo Source: Healthnotes, Inc.; www.healthnotes.com •
Alternative Therapy Acupuncture Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,663,00.html Alexander Technique Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,665,00.html Apitherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,669,00.html Aromatherapy Source: Integrative Medicine Communications; www.drkoop.com Aston-patterning Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10118,00.html Ayurveda Source: Integrative Medicine Communications; www.drkoop.com Bach Flower Remedies Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,673,00.html Biofeedback Source: Integrative Medicine Communications; www.drkoop.com Biofeedback Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,675,00.html Dance Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,687,00.html Hypnotherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
Alternative Medicine 129
Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,706,00.html Magnet Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,715,00.html Meditation Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,717,00.html Mind&body Medicine Source: Integrative Medicine Communications; www.drkoop.com Osteopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,724,00.html Qigong Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,729,00.html Reflexology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,730,00.html Reiki Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,731,00.html Relaxation Techniques Source: Integrative Medicine Communications; www.drkoop.com Rolfing Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,732,00.html Tai Chi Source: Integrative Medicine Communications; www.drkoop.com Traditional Chinese Medicine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10085,00.html
130 Chronic Pain
Yoga Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Amino Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10003,00.html Boswellia Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,759,00.html Bromelain Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,760,00.html Cayenne Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,765,00.html Devil's Claw Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,970,00.html Ginger Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,787,00.html Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Peppermint Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,812,00.html
Alternative Medicine 131
Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com SAMe (S-Adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html White Willow Bark Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10069,00.html
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
133
CHAPTER 4. DISSERTATIONS ON CHRONIC PAIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to chronic pain. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “chronic pain” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on chronic pain, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Chronic Pain ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to chronic pain. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Clinical Model of Pastoral Ministry to Persons in Chronic Pain by Mathew, Thomson Kuzhivelil, Dmin from Oral Roberts University, 1986, 270 pages http://wwwlib.umi.com/dissertations/fullcit/8621163
•
A Comparison of Coping Skills of Chronic, Non-malignant Pain Patients and Cancer Patients with Chronic Pain by Tice, Todd Allen; Phd from Texas Tech University, 2002, 79 pages http://wwwlib.umi.com/dissertations/fullcit/3043236
•
A Cultural Model of Chronic Pain Adaptation by Turner, Candice Corrigan, Phd from University of Kentucky, 1988, 321 pages http://wwwlib.umi.com/dissertations/fullcit/8814369
•
A Systematic Investigation of Contingent Consequences on Walking Exercise Performance of Chronic Pain Patients by Todd, Dennis Darrell, Phd from University of South Florida, 1988, 91 pages http://wwwlib.umi.com/dissertations/fullcit/8912383
134 Chronic Pain
•
Acute and Chronic Pain in Hemophilia Characteristic Pain Patterns and Coping Strategies by Choinière, Manon; Phd from Mcgill University (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL31369
•
An Exploratory Study of Prayer As a Coping Mechanism for Chronic Pain by Derose, Mouna El-khadiri; Ma from Roosevelt University, 2003, 39 pages http://wwwlib.umi.com/dissertations/fullcit/1411471
•
Anger Expression, Working Alliance, and Treatment Outcome Following Multidisciplinary Chronic Pain Treatment by Mirsky, Jeremy Evan; Phd from Illinois Institute of Technology, 2002, 118 pages http://wwwlib.umi.com/dissertations/fullcit/3074350
•
Attributional Style and Depression in Chronic Pain Patients Receiving Worker's Compensation Benefits (pain Management) by Mcguigan, Jane Boyer, Phd from University of Maryland College Park, 1992, 182 pages http://wwwlib.umi.com/dissertations/fullcit/9234621
•
Beyond Western Medicine: the Evaluation of Behavioral Medicine Techniques Within the Chronic Pain Population by Grimes, George Perry; Phd from Walden University, 2002, 113 pages http://wwwlib.umi.com/dissertations/fullcit/3059835
•
Biocultural Dimensions of Chronic Pain by Bates, Maryann Snow, Phd from University of Massachusetts, 1988, 437 pages http://wwwlib.umi.com/dissertations/fullcit/8906253
•
Chronic Pain and Quality of Life by White, Catherine Marie; Msc from University of Toronto (canada), 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74138
•
Chronic Pain As a Means of Communicating Alienation in American Society. Alienated Women and Their Pain: Thematic Case Studies by Brewer De Pozos, Kathleen Ann, Phd from University of California, Berkeley, 1980, 264 pages http://wwwlib.umi.com/dissertations/fullcit/8113237
•
Chronic Pain Clinics: an Example of the Rise in Entrepreneurial Medicine (medicine) by Behar, Joel, Phd from City University of New York, 1990, 192 pages http://wwwlib.umi.com/dissertations/fullcit/9020744
•
Chronic Pain, Suffering, and Spirituality: the Relationship between Chronic Pain, Suffering, and Different Religious Approaches by Meier, Levi, Phd from University of Southern California, 1981 http://wwwlib.umi.com/dissertations/fullcit/f460214
•
Chronic Pain: Coping Styles and Adjustment by Samie Khalajabadi, Simin; Phd from University of Houston, 2002, 47 pages http://wwwlib.umi.com/dissertations/fullcit/3042449
•
Clinically Relevant Aspects of Chronic Pain: Normal Personality Predictors by Nitch, Stephen Ray; Phd from Loma Linda University, 2002, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3042788
•
Cluster Analyses of Mmpi-2 Profiles in a Chronic Pain Sample: a Refined Method by Holly, Amanda; Ms from The Herman M. Finch U. of Health Sciences - the Chicago Medical Sch., 2002, 66 pages http://wwwlib.umi.com/dissertations/fullcit/1410258
Dissertations 135
•
Consideration of Meaning in the Assessment of Chronic Pain (pain Assessment) by Nikolaj, Sally, Phd from University of Alberta (canada), 1992, 192 pages http://wwwlib.umi.com/dissertations/fullcit/NN77404
•
Development of a Self-report Screening Instrument for Assessing Risk of Opioid Medication Misuse in Chronic Pain Patients by Adams, Laura Lee; Phd from The University of Texas Southwestern Medical Center at Dallas, 2002 http://wwwlib.umi.com/dissertations/fullcit/f927713
•
Effectiveness of a Clinical Intervention Program for Reduction of Pain, and Concomitant Symptoms of Anxiety, Depression, and Hostility in Individuals Experiencing Chronic Pain (rehabilitation) by Linzer, Marc Rubin, Phd from The University of Arizona, 1986, 109 pages http://wwwlib.umi.com/dissertations/fullcit/8704778
•
Effectiveness of Alternative Pain Management/acupuncture for Controlling Chronic Pain by Hajdaj, Diane E.; Ms from D'youville College, 2003, 106 pages http://wwwlib.umi.com/dissertations/fullcit/1413013
•
Effects of Brief, Intense Transcutaneous Electrical Stimulation on Chronic Pain by Jeans, Mary Ellen; Phd from Mcgill University (canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK31804
•
Evaluating Quality of Life, Functional Capabilities, and Coping Strategies of People with Chronic Pain Taking Opioids Versus No Opioids by Adams, Nancy Jane; Phd from The University of Wisconsin - Madison, 2002, 137 pages http://wwwlib.umi.com/dissertations/fullcit/3060552
•
Evaluation of a Multi-method Group Approach to the Management of Chronic Pain by Subramanian, Karen, Phd from The University of Wisconsin - Madison, 1985, 252 pages http://wwwlib.umi.com/dissertations/fullcit/8513484
•
Family Adaptability, Cohesion and Conflict in Families with Rheumatoid Arthritis, Chronic Pain and Depression by Caldwell, Karen Leigh, Phd from Virginia Polytechnic Institute and State University, 1988, 106 pages http://wwwlib.umi.com/dissertations/fullcit/8910943
•
Family-based Behavior Therapy with Pediatric Chronic Pain by Mcintyre, Samuel Brian, Edd from University of San Francisco, 1987, 163 pages http://wwwlib.umi.com/dissertations/fullcit/8802586
•
In the Company of Friends: the Organizational and Community Dimensions of Chronic Pain among Continuing Care Retirement Community Residents by Encandela, John Anthony, Phd from University of Pennsylvania, 1994, 148 pages http://wwwlib.umi.com/dissertations/fullcit/9427532
•
Individual Differences, Mood and Coping: a Process Analysis of Daily Chronic Pain by Newth, Sarah Jane; Phd from The University of British Columbia (canada), 2003, 117 pages http://wwwlib.umi.com/dissertations/fullcit/NQ79244
•
Is There a Relationship between Child Sexual Abuse and Chronic Pain? by Peacock, Patricia Lynn, Phd from The University of Tennessee, 1998, 257 pages http://wwwlib.umi.com/dissertations/fullcit/9923314
•
Locus of Control and Educationally Based Patient Care Outcomes in a Chronic Pain Center by Applegate, Margaret Helena, Edd from Indiana University, 1980, 257 pages http://wwwlib.umi.com/dissertations/fullcit/8103406
136 Chronic Pain
•
Meaning in Life As a Predictor of Outcome in Chronic Pain Patients: a Quantitative and Qualitative Study by Park, Kenneth; Phd from New School for Social Research, 2002, 95 pages http://wwwlib.umi.com/dissertations/fullcit/3062382
•
Measuring Subjective Well-being in Daily Life in Arthritis, Heart Disease, and Chronic Pain (health, Quality of Life) by Marnell, Margaret Esther, Phd from Stanford University, 1987, 277 pages http://wwwlib.umi.com/dissertations/fullcit/8707699
•
Multidimensional Assessment of People with Chronic Pain: a Critical Appraisal of the Person, Environment, Occupation Model by Schult, Marie-louise; Phd from Uppsala Universitet (sweden), 2002, 198 pages http://wwwlib.umi.com/dissertations/fullcit/f737697
•
Multivariate Clustering of Chronic Pain Patients: a Replication Using the Mmpi-2 by Nickel, James Allen, Phd from Ball State University, 1993, 141 pages http://wwwlib.umi.com/dissertations/fullcit/9332552
•
Partners in Pain: the Relationship between Spousal Locus-of-control and Chronic Pain Patients' Coping Behavior by Murphy, James Patrick, Phd from California School of Professional Psychology - Fresno, 1993, 99 pages http://wwwlib.umi.com/dissertations/fullcit/9419460
•
Patterning of Pain and Power with Guided Imagery: an Experimental Study with Persons Experiencing Chronic Pain by Lewandowski, Wendy Ann; Phd from Case Western Reserve University (health Sciences), 2002, 169 pages http://wwwlib.umi.com/dissertations/fullcit/3061312
•
Perceived Parental Care and Protection As Correlates of Chronic Pain in Adults (parental Care) by Walberer, Daniel Lee, Edd from Western Michigan University, 1992, 74 pages http://wwwlib.umi.com/dissertations/fullcit/9229591
•
Prediction of Chronic Pain Clinic Outcome Using Psychometric and Demographic Predictors by Lyman, Douglas Robert, Phd from Marquette University, 1988, 112 pages http://wwwlib.umi.com/dissertations/fullcit/8904272
•
Psychological and Demographic Variables Related to Duration of Pain in Chronic Pain Syndrome by Wittenauer, Deborah Ann, Phd from The University of Akron, 1988, 164 pages http://wwwlib.umi.com/dissertations/fullcit/8814397
•
Psychosocial and Medical Factors in Discriminating among Return-to-work Groups in a Chronic Pain Population: a Test of the Biopsychosocial Model by Schumacher, Nicole Tosi; Phd from The University of Akron, 2002, 203 pages http://wwwlib.umi.com/dissertations/fullcit/3049876
•
Psychosocial Assessments As Predictors of Treatment Outcome in a Chronic Pain Population Presenting to a Multidisciplinary Pain Management Centre by Zarb, John Paul; Msc from University of Toronto (canada), 2002, 86 pages http://wwwlib.umi.com/dissertations/fullcit/MQ68719
•
Relationship Systems: Exploring the Role of the Emotional System in Understanding Dual Chronic Pain Couples by Boyd, Tommie Vannoy; Phd from Nova Southeastern University, 2000, 314 pages http://wwwlib.umi.com/dissertations/fullcit/9977050
Dissertations 137
•
Relationships among Factors Underlying Functioning with Chronic Pain and Risk of Suicide by Hargis, David Lee, Phd from University of New Orleans, 1995, 147 pages http://wwwlib.umi.com/dissertations/fullcit/9701557
•
Self-schema Functioning and Its Relationship to Depression and Treatment Outcome among Chronic Pain Patients by Quek, Jonathan S; Phd from York University (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39320
•
Social Work and Chronic Pain: a Canadian Study of Medical Social Workers by Sieppert, Jackie Dale, Phd from Arizona State University, 1994, 204 pages http://wwwlib.umi.com/dissertations/fullcit/9516257
•
The Chronic Pain Experience: Management of the Impaired Self by Kotarba, Joseph Anthony, Phd from University of California, San Diego, 1980, 356 pages http://wwwlib.umi.com/dissertations/fullcit/8023102
•
The Church's Ministry with Those Who Suffer Chronic Pain by Hudson, Sara Luo, Dmin from Drew University, 1996, 73 pages http://wwwlib.umi.com/dissertations/fullcit/9626926
•
The Effect of Chronic Pain on Reading Comprehension by Rankin, Margaret Ann, Phd from The University of Iowa, 1990, 347 pages http://wwwlib.umi.com/dissertations/fullcit/9112473
•
The Effects of a Treatment Program for Chronic Pain Patients Using Enjoyable Imagery with Biofeedback Induced Relaxation by Mckee, Patrick James, Phd from University of Oregon, 1981, 100 pages http://wwwlib.umi.com/dissertations/fullcit/8123496
•
The Effects of Antecedent and Temporal Variables of Self-report Measures of Chronic Pain by White, Barbara A., Phd from The University of Utah, 1983, 58 pages http://wwwlib.umi.com/dissertations/fullcit/8325938
•
The Efficacy of Comprehensive Behavior Therapy for Chronic Pain by Sookman, Deborah A; Phd from Concordia University (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37113
•
The Experience of Adjustment to Chronic Pain by Whillans, Penny J; Edd from University of Toronto (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39278
•
The Family Physician Experience of Treating Chronic Pain Patients Whose Pain Has Complex Etiology: a Qualitative Study by Drysdale, Susan Maxine; Phd from Saybrook Graduate School and Research Center, 2003, 189 pages http://wwwlib.umi.com/dissertations/fullcit/3090297
•
The Influence of a Cognitive-behavioral Treatment Program on Chronic Pain Patients by Walczyk, Maureen A.; Ms from Michigan State University, 2002, 101 pages http://wwwlib.umi.com/dissertations/fullcit/1409565
•
The Intervention of Music on Perceptions of Chronic Pain, Depression, and Anxiety in Ambulatory Individuals with Cancer by Flaugher, Marquetta; Dsn from The University of Alabama at Birmingham, 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3066311
138 Chronic Pain
•
The Measurement of Nociceptive Peptides for the Assessment of Acute and Chronic Pain in the Medicolegal Investigation of Violent Death by Quarino, Lawrence A.; Phd from City University of New York, 2000, 333 pages http://wwwlib.umi.com/dissertations/fullcit/9969721
•
The Measurement of Subjective Well-being in Persons with Chronic Pain Subsequent to Occupational Injuries by Shirley, Edwin Rankin, Phd from The University of Wisconsin - Madison, 1995, 196 pages http://wwwlib.umi.com/dissertations/fullcit/9608177
•
The Nature of Trait Empathy in Clients with Chronic Pain and Their Counselors and Its Impact on the Development of the Working Alliance and Outcome (empathy) by Forman, Nancy Walker, Phd from The Ohio State University, 1990, 299 pages http://wwwlib.umi.com/dissertations/fullcit/9022497
•
The Relationship between Psychological Distress and Coping in a Spinal Cord Injury Population with Severe Chronic Pain by Bartok, Cynthia Elizabeth; Phd from Pacific Graduate School of Psychology, 2002, 150 pages http://wwwlib.umi.com/dissertations/fullcit/3038057
•
The Relationship of Antidepressant Use, Depression, Depressive Symptomatology and Reported Pain to Multidisciplinary Chronic Pain Treatment Outcome Measures by Knuppel, Maurie Lane, Phd from Virginia Polytechnic Institute and State University, 1996, 156 pages http://wwwlib.umi.com/dissertations/fullcit/9626121
•
The Relationship of Patient's Perceived Level of Chronic Pain Intensity, and Spouse and Patient Somatizing in Marital Adjustment by Steele, William Robert, Phd from Brigham Young University, 1988, 109 pages http://wwwlib.umi.com/dissertations/fullcit/8908595
•
The Role of Education in the Treatment of Chronic Pain Patients: a Quantitative Study of Factors That Influence the Self-management of Chronic Pain by Agan, Donna L.; Edd from University of San Diego, 2001, 182 pages http://wwwlib.umi.com/dissertations/fullcit/3007286
•
The Role of Problem-solving in the Adaptation of Women to Chronic Pain by Banerjee, Shibany Preeya; Phd from Central Michigan University, 2002, 84 pages http://wwwlib.umi.com/dissertations/fullcit/3066206
•
The Treatment of Chronic Pain Patients Via a Structured Group Counseling Approach. by Nesbit, Michael, Edd from University of South Dakota, 1978, 112 pages http://wwwlib.umi.com/dissertations/fullcit/7904896
•
'To Get Back into Society the Way I Was': a Sociological Analysis of Physical Disability and Impairment (dialectics, Deafness, Chronic Pain) by Seidel, John Vail, Phd from University of Colorado at Boulder, 1984, 419 pages http://wwwlib.umi.com/dissertations/fullcit/8422650
•
Transition from Acute to Chronic Pain: a Biopsychosocial Model of Chronicity by Young, Corinna W.; Phd from Alliant International University, San Diego, 2002, 169 pages http://wwwlib.umi.com/dissertations/fullcit/3064184
•
Trauma and Chronic Pain by Catanese, Sarah Pavin; Ms from The Herman M. Finch U. of Health Sciences - the Chicago Medical Sch., 2002, 60 pages http://wwwlib.umi.com/dissertations/fullcit/1410254
Dissertations 139
•
Workers with Chronic Pain: Recovery and Reintegration by Augello, Jean D. Bass; Phd from The University of Utah, 2002, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3041618
•
Worldviews and Health Care Choices among People with Chronic Pain by Buck, Ernestina Suzanne; Phd from The University of Arizona, 2002, 97 pages http://wwwlib.umi.com/dissertations/fullcit/3061016
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
141
CHAPTER 5. CLINICAL TRIALS AND CHRONIC PAIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning chronic pain.
Recent Trials on Chronic Pain The following is a list of recent trials dedicated to chronic pain.8 Further information on a trial is available at the Web site indicated. •
Chronic Pain after Amputation Condition(s): Amputation, Traumatic; Pain; Postoperative Pain Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: This trial will test the effectiveness of amitriptyline in relieving chronic pain of adults that have had an amputation Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006427
•
Treatment of Chronic Pain after Spinal Cord Injury (SCI) or Amputation Condition(s): Spinal Cord Injuries; Amputation, Traumatic; Pain Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Pain is a major problem for people after spinal cord injuries and amputations. This is a study to test how pain is affected by adding methadone to a sixweek program of weekly physical therapy, relaxation training and counseling.
8
These are listed at www.ClinicalTrials.gov.
142 Chronic Pain
Individuals who qualify for this study will receive a comprehensive medical and physical therapy evaluation. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006448 •
A Multicenter Phase II/III, Placebo-Controlled Study of SNX-111 Administered Intrathecally to Cancer and AIDS Patients With Chronic Pain Condition(s): HIV Infections; Pain Study Status: This study is completed. Sponsor(s): Neurex Purpose - Excerpt: To determine the safety and efficacy of SNX-111 in controlling severe, chronic pain in cancer and AIDS patients. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002160
•
Chronic Pain in Spinal Cord Injury Condition(s): Spinal Cord Injuries; Pain Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: This trial tests the effectiveness of the drug amitriptyline vs placebo to relieve chronic pain in adults that have had a spinal cord injury. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006428
•
Prialt (ziconotide) In Severe Chronic Pain Condition(s): Pain Study Status: This study is completed. Sponsor(s): Elan Pharmaceuticals Purpose - Excerpt: The purpose of this study is to understand the effects of intrathecal ziconotide (an experimental pain medication) when the dose is slowly increased over a 3-week period in patients with severe chronic pain. During the weaning phase, the study will also gather information about switching from other intrathecal or IT medication (slowly pumped directly into the space around the spine) to other systemic pain medication (by mouth or through the skin using a patch). After being weaned off current IT medication, patients will be placed on IT ziconotide or placebo (non-active substance) as well as being allowed a stable dose of systemic pain medications. Patients who complete this study may be eligible for long-term ziconotide therapy via extension protocol ELN92045-352.
Clinical Trials 143
Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047749 •
Treatment for Chronic Pain in Patients With Advanced Cancer Condition(s): AIDS-Related Lymphoma; Hodgkin's Disease; Non-Hodgkin's Lymphoma; Digestive System Cancer; Lymphoid Cancer; Leukemia; Pain Study Status: This study is completed. Sponsor(s): National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Different drug formulations and combinations of drugs may help patients with chronic pain live more comfortably. It is not yet known which regimen is most effective for chronic pain. PURPOSE: Randomized double blinded phase III trial to compare the effectiveness of different morphine formulations with or without dextromethorphan in treating patients with chronic pain from advanced cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003687
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “chronic pain” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
•
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
•
For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
•
For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
144 Chronic Pain
•
For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
•
For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
•
For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
•
For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
•
For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
•
For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
•
For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
•
For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
•
For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
•
For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
•
For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
145
CHAPTER 6. PATENTS ON CHRONIC PAIN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “chronic pain” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on chronic pain, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Chronic Pain By performing a patent search focusing on chronic pain, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
146 Chronic Pain
example of the type of information that you can expect to obtain from a patent search on chronic pain: •
2-substituted piperidine analogs and their use as subtype-selective NMDA receptor antagonists Inventor(s): Bigge; Christopher F. (Ann Arbor, MI), Cai; Sui Xiong (Foothill, CA), Guzikowski; Anthony P. (Eugene, OR), Keana; John F. W. (Eugene, OR), Lan; Nancy C. (South Pasadena, CA), Weber; Eckard (Laguna Beach, CA), Woodward; Richard (Aliso Viejo, CA) Assignee(s): Cocensys, Inc. (Irvine, CA), Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,124,317 Date filed: November 18, 1998 Abstract: Novel 2-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 2-substituted piperidine analogs as selectively active antagonists of N-methyl-D-aspartatc (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, amioglycoside antibiotics-induced hearing loss, migraine headaches, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described. Excerpt(s): This invention is related to 2-substituted piperidine analogs. The analogs are selectively active as antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 2-substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neurodegenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Ar is aryl or heteroaryl, each of which may be optionally substituted. 2-[2-(3,4-Dichlorophenoxy)ethyl]-1-cinnamylpiperidine oxalate hemihydrate and 4-[2-(2-Dibenzofuranyloxy)ethyl]-1-cinnamylpiperidine oxalate are exemplified. The compounds of this reference are said to be useful for treating anoxia, ischaemia, such as stroke, migraine, epilepsy, traumatic head injury, AIDS-related dementia, neurodegenerative diseases and drug addiction withdrawal. This reference does not disclose or suggest NMDA receptor activity, let alone selective NMDA receptor subtype antagonism. Web site: http://www.delphion.com/details?pn=US06124317__
Patents 147
•
4-substituted piperidine analogs and their use as subtype selective NMDA receptor antagonists Inventor(s): Bigge; Christopher F. (Ann Arbor, MI), Cai; Sui Xiong (Foothill, CA), Guzikowski; Anthony P. (Eugene, OR), Keana; John F. W. (Eugene, OR), Lan; Nancy C. (South Pasadena, CA), Weber; Eckard (Laguna Beach, CA), Woodward; Richard (Aliso Viejo, CA), Yuen; Po-Wai (Ann Arbor, MI), Zhou; Zhang-Lin (Irvine, CA) Assignee(s): Cocensys, Incorporated (Irvine, CA), Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,124,323 Date filed: September 16, 1998 Abstract: Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs are selective active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, psychosis, anxiety, migraine headaches, glaucoma, CMV retinitis, aminoglycoside antibiotics-induced hearing loss, convulsions, chronic pain, opioid tolerance or withdrawal, urinary incontinence or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described. Excerpt(s): This invention is related to 4-substituted piperidine analogs, including hydroxypiperidine and tetrahydropyridine analogs. The analogs are selectively active as antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 4-substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, psychosis, glaucoma, CMV retinitis, urinary incontinence, aminoglycoside antibiotics-induced hearing loss, convulsions, migraine headache, chronic pain, opioid tolerance or withdrawal, or neuro-degenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Other piperidine derivatives having aryl alkanol functionality are disclosed by PCT International Publication No. WO 93/11107 (for treating hypoxia and ischaemia), International Publication No. WO 94/10166 (for treating stroke, addiction, pain, epilepsy, psychosis, traumatic brain injury and CNS degenerative diseases), EP 0398578 (for treating stroke or CNS degenerative diseases, Alzheimer's disease, Huntington's disease and Parkinson's disease) and PCT International Publication No. WO 93/02052 (for treating stroke, traumatic injury to the brain and spinal cord, and neuronal degenerative diseases). Similar to EP 0648744, each of these references requires a piperidine derivative having an alkyl hydroxy or keto group alpha to the aryl group of the N-1 substituent. The 4-substituted piperidine analogs of this invention differ in kind from the piperidine derivatives of these references. Web site: http://www.delphion.com/details?pn=US06124323__
148 Chronic Pain
•
Alkyl, azido, alkoxy and fluoro-substituted and fused quinoxalinediones and the use thereof as glycine receptor antagonist Inventor(s): Cai; Sui Xiong (Irvine, CA), Keana; John F. W. (Eugene, OR), Kher; Sunil (Eugene, OR), Weber; Eckard (Laguna Beach, CA) Assignee(s): CoCensys, Inc. (Irvine, CA), State of Oregon, Acting by and Through the Oregon State Board of Higher (Eugene, OR), The Regents of the University of California (Oakland, CA) Patent Number: 6,147,075 Date filed: August 18, 1999 Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, and inducing anesthesia are disclosed by administering to an animal in need of such treatment an alkyl or azido-substituted 1,4dihydroquinoxaline-2,3-dione or pharmaceutically acceptable salts thereof, which have high binding to the glycine receptor. Excerpt(s): The present invention is in the field of medicinal chemistry and relates to compounds that have a high affinity for the glycine binding site, lack PCP side effects, and cross the blood brain barrier at high levels. In particular, the present invention relates to novel alkyl, azido, alkoxy, fluoro-substituted, and fused 1,4dihydroquinoxaline-2,3-diones and their use to treat or prevent neuronal degeneration associated with ischemia, pathophysiologic conditions associated with neuronal degeneration, convulsions, anxiety, chronic pain, and to induce anesthesia. Glutamate is thought to be the major excitatory neurotransmitter in the brain. There are three major subtypes of glutamate receptors in the CNS. These are commonly referred to as kainate, AMPA, and N-methyl-D-aspartate (NMDA) receptors (Watkins and Olverman, Trends in Neurosci. 7:265-272 (1987)). NMDA receptors are found in the membranes of virtually every neuron in the brain. NMDA receptors are ligand-gated cation channels that allow Na.sup.+, K.sup.+, and Ca.sup.++ to permeate when they are activated by glutamate or aspartate (non-selective, endogenous agonists) or by NMDA (a selective, synthetic agonist) (Wong and Kemp, Ann. Rev. Pharmacol. Toxicol. 31:401-425 (1991)). Glutamate alone cannot activate the NMDA receptor. In order to become activated by glutamate, the NMDA receptor channel must first bind glycine at a specific, high affinity, glycine binding site that is separate from the glutamate/NMDA binding site on the receptor protein (Johnson and Ascher, Nature 325:329-331 (1987)). Glycine is therefore an obligatory co-agonist at the NMDA receptor/channel complex (Kemp, J. A., et al., Proc. Natl. Acad. Sci. USA 85:6547-6550 (1988)). Web site: http://www.delphion.com/details?pn=US06147075__
Patents 149
•
Anticonvulsant drugs and pharmaceutical compositions thereof Inventor(s): Bialer; Meir (Jerusalem, IL), Dagan; Arie (Jerusalem, IL), Sherbel; Sussan (Tarshicha, IL) Assignee(s): Yissum Research Development Company of the Hebrew University of Jerusalem () Patent Number: 6,028,102 Date filed: February 24, 1998 Abstract: According to the present invention, anticonvulsant compounds N-acetyl,N'benzylglycinamide and N-benzyloxycarbonylglycinamide-Z-glycinamide are disclosed. The present invention also discloses an anticonvulsant pharmaceutical composition comprising an effective amount of at least one active ingredient selected from Nacetyl,N'-benzylglycinamide and N-benzyloxycarbonylglycinamide-Z-glycinamide and a pharmaceutically acceptable carrier or diluent. The present invention provides a method of controlling convulsions in a mammal by administering to the mammal an effective amount of antiepileptic compounds N-acetyl,N'-benzylglycinamide or Nbenzyloxycarbonylglycinamide-Z-glycinamide. Combinations of the anticonvulsion compounds can also be administered. The convulsions may be due to epilepsy, febrile convulsions or convulsions precipitated by irritative lesions in the brain. Further the composition may be used to prevent migraine and to treat chronic pain and bipolar disorder. Excerpt(s): The present invention relates to new anticonvulsants drugs and pharmaceutical compositions containing the anticonvulsants drugs and methods of treating with the drugs. Lambert et al. [1994] reported that a glycine derivative Nbenzyloxy-carbonylglycine (Z-glycine) was found to be far more active than glycine in rats following chemically and electrically induced seizures. Subsequently, the anticonvulsant activity of ester and amide-type lipid conjugates of glycine and Nbenzyloxycarbonylglycine (Z-glycine) were evaluated utilizing the maximal electroshock (MES) and the strychnine tests [Lambert et al, 1996]. In all cases the Zglycine derivatives were always more potent than the corresponding glycine derivatives with the amide lipid being more active than the ester derivatives [Lambert et al, 1996]. Applicants recently explored the pharmacokinetics and pharmacodynamics (anticonvulsant activity and neurotoxicity) of N-phthaloyl and N-valproyl derivatives of GABA and glycine [Salach et al, 1994; Hadad and Bialer, 1995; U.S. Pat. No. 5,585,358]. Out of the valproyl derivatives only valproyl glycinamide showed a good anticonvulsant activity in both mice and rats due to its better pharmacokinetic profile [Hadad and Bialer, 1995]. N-valproyl glycinamide (TV 1901) is currently undergoing phase I clinical trials [Bialer et al, 1996A]. Subsequently, applicants developed and evaluated analogues and isomers of TV 1901 which showed good anticonvulsant activity in rodents such as tetramethylcyclopropylcarbonyl glycinamide [Bialer et al, 1996B], N-2-enevalproyl glycinamide, valnoctyl glycinamide and diisopropyl acety glycinamide [Hadad and Bialer, 1997]. These four derivatives of TV 1901 showed, in mice and rats, similar anticonvulsant activity and safety margins to that of the parent compound. Web site: http://www.delphion.com/details?pn=US06028102__
150 Chronic Pain
•
Branched chain amino acid-dependent aminotransferase inhibitors and their use in the treatment of neurodegenerative diseases Inventor(s): Hays; Sheryl Jeanne (Ann Arbor, MI), Hu; Lain-Yen (Ann Arbor, MI), Lei; Huangshu (Ann Arbor, MI), Scholten; Jeffrey David (Ann Arbor, MI), Wustrow; David Juergen (Ann Arbor, MI) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,632,831 Date filed: November 26, 2002 Abstract: The invention relates to BCAT inhibitors and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions, aminoglycoside antibioticsinduced hearing loss, migraine headache, chronic pain, neuropathic pain, Parkinson's disease, diabetic retinopathy, glaucoma, CMV retinitis, urinary incontinence, opioid tolerance or withdrawal, and inducing anesthesia, as well as for enhancing cognition. Excerpt(s): This invention is related to branched chain amino acid-dependent amino transferase (BCAT) inhibitors. The invention is also directed to the use of BCAT inhibitors as neuro-protective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, chronic pain, neuropathic pain, glaucoma, CMV retinitis, diabetic retinopathy, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neuro-degenerative disorders such as lathyrism, Alzheimer's disease, Parkinsonism, amyotrophic lateral sclerosis (ALS), and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's disease, Parkinson's disease, and Huntington's disease. Excitatory amino acid receptor antagonists that block NMDA receptors are recognized for usefulness in the treatment of disorders. NMDA receptors are intimately involved in the phenomenon of excitotoxicity, which may be a critical determinant of outcome of several neurological disorders. Disorders known to be responsive to blockade of the NMDA receptor include acute cerebral ischemia (stroke or cerebral trauma, for example), muscular spasm, convulsive disorders, neuropathic pain and anxiety, and may be a significant causal factor in chronic neurodegenerative disorders such as Parkinson's disease (Klockgether T., Turski L., Ann. Neurol., 1993;34:585-593), human immunodeficiency virus (HIV) related neuronal injury, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (Francis P. T., Sims N. R., Procter A. W., Bowen D. M., J. Neurochem., 1993;60(5):1589-1604, and Huntington's disease (see Lipton S., TINS, 1993;16(12):527-532; Lipton S. A., Rosenberg P. A., New Eng. J. Med., 1994;330(9):613-622; and Bigge C. F., Biochem. Pharmacol., 1993;45:15471561, and referenced cited therein.) NMDA receptor antagonists may also be used to
Patents 151
prevent tolerance to opiate analgesia or to help control withdrawal symptoms from addictive drugs (Eur. Pat. Appl. 488,959A). Web site: http://www.delphion.com/details?pn=US06632831__ •
Dextromethorphan and oxidase inhibitor for weaning patients from narcotics and anti-depressants Inventor(s): Smith; Richard A. (7569 Cabrillo Ave., La Jolla, CA 92037) Assignee(s): none reported Patent Number: 6,207,674 Date filed: December 22, 1999 Abstract: Patients can be helped to break free of addictive or habit-forming narcotics and anti-depressants, by treatment using two drugs. One drug is dextromethorphan (DM), which has been used for decades as an anti-tussive (cough-suppressing) drug in cough syrups. The other drug is an oxidase inhibitor which suppresses activity of a liver enzyme called cytochrome P450-2D6 (also called debrisoquin hydroxylase, sparteine monooxygenase, cytochrome P450-DB, and CYP2D6). In most patients, this oxidase enzyme rapidly degrades DM and converts it into a metabolite called dextrorphan. An oxidase inhibitor (such as quinidine) which suppresses cytochrome P450-2D6 activity increases the half-life and concentration of DM in the circulating blood. When this combined treatment was administered orally to patients who had become dependent on morphine and anti-depressant drugs because of chronic intractable pain, it initially helped the patients reduce their dosages of morphine and other drugs, including antidepressants. When additional testing was done, the combined treatment allowed patients to entirely terminate all use of morphine and anti-depressants, with minimal withdrawal or other adverse effects. Importantly, these same patients received no substantial benefit from taking dm by itself, without an oxidase inhibitor. Accordingly, the combination of dextromethorphan plus an anti-oxidase drug can allow at least some patients to break entirely free of narcotics and/or anti-depressants, even after years of use for chronic pain and other medical problems, even when they are not substantially helped by dextromethorphan alone. Excerpt(s): This invention is in the field of pharmacology, and relates to drug treatments for reducing the dependence of patients on habit-forming and potentially addictive drugs, including narcotics and anti-depressants. The term "narcotic" as used herein has the same meaning used in standard medical reference works, such as the "more recent" definitions used in Stedman's Medical Dictionary, 26th edition (Williams & Wilkins Publ., Baltimore, 1995) and in the "Analgesics" chapter in the "Drug Evaluations" subscription service published by the American Medical Association (Chicago). Briefly, "narcotics" as used in any definition (either classical or recent) includes: (1) opiate drugs, defined as any preparation or derivative of opium, a natural mixture derived from poppy plants that includes a number of medically important and/or habit-forming or addictive drugs, including morphine, codeine, noscapine, papaverine, thebaine, and heroin; and, (2) opioid drugs, which includes opiates as well as various synthetic narcotic drugs having similar or related chemical structures and effects. Such synthetic narcotics include meperidine (sold under trademarks such as DEMEROL.TM.), hydrocodone (sold under trademarks such as VICODIN.TM.), hydromorphone (sold under trademarks such as DILAUDID.TM.), propoxyphene (sold under trademarks such as DARVON.TM.), oxycodone (sold under trademarks such as PERCODAN.TM. when mixed with aspirin, or PERCOCET.TM. when mixed with acetaminophen),
152 Chronic Pain
levorphanol, fentanyl, and methadone. Under a more recent definition that has come to be accepted within the medical profession, the term "narcotics" has been broadened somewhat, to include other synthetic drugs which have "effects that are similar to opium and its derivatives". In order for a drug to be to classified as a "narcotic", its effects must include: (1) the ability to induce "significant alteration of mood and behavior"; (2) the ability to induce a condition of "stuporous analgesia"; and (3) a substantial risk of dependence, tolerance, and/or addiction. Web site: http://www.delphion.com/details?pn=US06207674__ •
Epidural nerve root stimulation Inventor(s): Alo; Kenneth M. (4512 Teas, Bellaire, TX 77401), Feler; Claudio A. (950 Audubon Dr., Memphis, TN 38117) Assignee(s): none reported Patent Number: 6,002,964 Date filed: July 15, 1998 Abstract: A method of managing chronic pain produced by a variety of disorders or conditions which afflict the pelvic region and which is transmitted through the lumbosacral region of the human body. The method includes techniques for positioning one or more stimulation leads within or about the sacrum to enable electrical energy to be applied to spinal nervous tissue, including nerve roots, to inhibit the transmission of pain. Excerpt(s): The present invention relates to a method of managing human chronic pain due to disease, nervous disorders, or like afflicting the pelvic region, and in particular, to a method of applying electrical energy through electrical stimulation electrodes particularly positioned in the lumbosacral region of a patient to inhibit the transmission of chronic pain signals to the brain. Interstitial cystitis (IC) is a chronic inflammatory condition of unknown etiology which affects the mucosa and the muscularis of the bladder. IC is estimated to affect 450,000 people, 90% being women. Because of the lack of understanding of the disorder, pain management for IC is difficult. Common pain management practices currently include administering analgesic medications. For mild to moderate pain, acetaminophen, aspirin, or other nonsteroidal, antiinflammatory agents are utilized. For more severe pain, opioid medications (for example, morphine, hydromorphone, levorphanol, methadone, fentanyl, oxycodone, and hydrocodone) may be used. Of course, while opioids may provide some temporary relief, physicians must be concerned about potential side effects and the development of patient addictions. Web site: http://www.delphion.com/details?pn=US06002964__
•
Epidural nerve root stimulation with lead placement method Inventor(s): Alo; Kenneth M. (4512 Teas, Bellaire, TX 77401), Feler; Claudio A. (350 Sweetbriar Rd., Memphis, TN 38120) Assignee(s): none reported Patent Number: 6,104,957 Date filed: August 21, 1998
Patents 153
Abstract: A method of managing chronic pain and/or symptoms of motor dysfunction produced by a variety of disorders or conditions. The method includes techniques for positioning one or more stimulation leads so as to enable delivery of electrical energy to epidural spinal nervous tissue, spinal ganglia, nerve plexi, or peripheral nerves using superior-to-inferior and/or trans-spinal advancement relative to a vertebral column and stimulating selected spinal nervous tissue. Excerpt(s): The present invention relates to a method of managing human chronic pain and/or controlling symptoms of motor dysfunction, and in particular, to a method of applying electrical energy through electrical stimulation electrodes particularly positioned along certain spinal nervous tissue to inhibit or interfere with the transmission of signals along spinal neural pathways 10 related to chronic pain and/or motor dysfunction. Application of specific electrical energy to the spinal cord for the purpose of managing pain has been actively practiced since the 1960s. While a precise understanding of the interaction between the applied electrical energy and the nervous tissue is not fully appreciated, it is known that application of an electrical field to spinal nervous tissue can effectively mask certain types of pain transmitted from regions of the body associated with the stimulated tissue. More specifically, applying particularized electrical pulses to the spinal cord associated with regions of the body afflicted with chronic pain can induce paresthesia, or a subjective sensation of numbness or tingling, in the afflicted bodily regions. This paresthesia can effectively inhibit the transmission of non-acute pain sensations to the brain. Electrical energy, similar to that used to inhibit pain perception, may also be used to manage the symptoms of various motor disorders, for example, tremor, dystonia, spasticity, and the like. Motor spinal nervous tissue, or nervous tissue from ventral nerve roots, transmits muscle/motor control signals. Sensory spinal nervous tissue, or nervous tissue from dorsal nerve roots, transmit pain signals. Corresponding dorsal and ventral nerve roots depart the spinal cord "separately"; however, immediately thereafter, the nervous tissue of the dorsal and ventral nerve roots are mixed, or intertwined. Accordingly, electrical stimulation intended to manage/control one condition (for example, pain) often results in the inadvertent interference with nerve transmission pathways in adjacent nervous tissue (for example, motor nerves). Web site: http://www.delphion.com/details?pn=US06104957__ •
Heat cells Inventor(s): White; Richard Keim (Maineville, OH) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 5,984,995 Date filed: March 29, 1996 Abstract: This invention relates to a method of manufacturing heat cells which are based on a specific iron oxidation chemistry and having specific physical dimensions and fill characteristics. This method uses direct compaction of powdered ingredients into granules, pellets, tablets, slugs, and/or the like. These heat cells, which can be incorporated into disposable body wraps, provide a controlled and sustained temperature for consistent, convenient, and comfortable heat application for treating temporary or chronic pain. This invention also relates to said exothemic compositions incorporated into said heat cells.
154 Chronic Pain
Excerpt(s): This invention relates to a method of manufacturing heat cells which incorporate exothermic compositions comprising dry-compacted heating elements such as granules, pellets, tablets, slugs, and the like. These heat cells can be easily incorporated into disposable body wraps and the like, which adapt to a wide variety of body contours, providing consistent, convenient, and comfortable heat application to the wearer. This invention also relates to said exothemic compositions incorporated into said heat cells. A common method of treating temporary or chronic pain is by application of heat to the afflicted area. Such heat treatments are used as a means of therapy for conditions which include aches, stiffness in muscles and joints, nerve pain, rheumatism and the like. These treatments include the use of whirlpools, hot towels, hydrocollators, heating pads and elastic compression bands. Many of these devices employ reusable thermal packs containing, e.g., water and microwaveable gels. In general, such devices which require the thermal source to be replenished are inconvenient to use. Further, many of these thermal units or devices do not provide long lasting heat and also do not maintain a consistent temperature over long periods of time. The skin temperature needs to be maintained from about 38.degree. C. to about 41.degree. C. but not above 45.degree. C., as tissue damage occurs above 45.degree. C., to achieve the desired therapeutic benefits. The beneficial therapeutic effects from this administration of heat diminishes after the heat source is removed; therefore, it is desirable to provide a sustained heat source to the afflicted area for as long as possible, preferably for about eight hours. Disposable heat packs based on iron oxidation, such as those described in U.S. Pat. Nos. 4,366,804, 4,649,895, 5,046,479, and Re. 32,026 are known and can provide long-lasting heat. However, such devices have proven not totally satisfactory. Many of these devices cannot maintain a consistent and controlled temperature and/or such thermal devices are bulky and have unsatisfactory physical dimensions which hinder their effectiveness. Specifically, such devices cannot be easily incorporated into wraps which can comfortably conform to various body contours and hence deliver inconsistent, inconvenient and/or uncomfortable heat application to the body. Web site: http://www.delphion.com/details?pn=US05984995__ •
Heat pipe nerve cooler Inventor(s): Dobak, III; John D. (La Jolla, CA) Assignee(s): Innercool Therapies, inc. (San Diego, CA) Patent Number: 6,364,899 Date filed: June 9, 1999 Abstract: The invention provides a method and apparatus for producing reversible focal hypothermia of the nervous system to control chronic pain. Nerve conduction is blocked by mild cooling (0 to 25.degree. C.), or hypothermia. At these temperatures, nerve tissue is not destroyed and recovers completely when cooling is terminated, such that the treatment is reversible. By blocking conduction in pain nerves, pain sensation is eliminated in a manner analogous to drugs such as lidocaine that also block nerve conduction to provide anesthesia. The invention can be applied to a variety of conditions such as urge incontinence, muscle spasticity, and epilepsy. Many of these disorders are mediated by nerve and nervous tissue that could be interrupted by cooling. In addition, neurologic dysfunction found in multiple sclerosis may improve by cooling of the nerves. The method and apparatus may be used to cool areas of the nervous system affected by multiple sclerosis to allow more normal functions.
Patents 155
Excerpt(s): Not Applicable. A number of types of nerves are disposed within the posterior gray horn 16. Two types of pain sensing nerves have been identified: A.sub.delta. and C. Referring to FIGS. 2 and 3, A.sub.delta. fibers 18 are disposed within regions I and V and the same produce a rapid initial and intense response to painful stimuli. C fibers 20 are disposed within region II and produce a more blunted but prolonged response. C fibers 20 are believed to be responsible for many chronic pain syndromes. Pain is conducted via fibers of the peripheral nervous system to the central nervous system, or nerves in the spinal cord. The pain signal is conducted up nerve tracts of the spinal cord to the pain sensing areas of the brain (i.e., the thalamus). The transmission of the pain signal from the peripheral nerves to the central nerves takes place in the synapses of the posterior gray horn region 16 of the spinal cord 12. A synapse is a neuron-to-neuron transmission of a signal by a chemical mediator that traverses a small gap between two axon terminals. Web site: http://www.delphion.com/details?pn=US06364899__ •
Heatbeam dolorimeter Inventor(s): Lipman; Jonathon J. (Libertyville, IL) Assignee(s): Neuroscience Toolworks, Inc. (Evanston, IL) Patent Number: 6,248,079 Date filed: December 2, 1999 Abstract: A portable dolorimeter arrangement for determining a subject's cutaneous pain tolerance level at any site on the body allows for chronic pain diagnosis, and for the diagnosis of subtle sensory abnormalities. The arrangement comprises a heat projector (9) and an IR thermopile (19) focused on the same area of the subject's skin. The heat projector (9) is controlled via an interface (22) by a lap top computer (4) which performs acquisition, processing, display and storage of pain tolerance latency data. Excerpt(s): The present invention relates to neurological diagnostic tools. More particularly, the present invention relates to an improved radiant heatbeam dolorimeter for determining a subject's cutaneous pain tolerance level at any site on the body. Pain is the single most common symptom for which patients seek medical treatment and there is currently no objective method available for its measurement. Present methods of quantifying "pain" are little more than lexicons for its verbal description or biomechanical methods for measuring the restriction of a particular range of motion or activities of daily living associated with the pain. Some psychometric methods attempt to quantify the personality or cognitive distortions from which the pain patient suffers. In no case, however, do these methods reveal the covert and subjective sensory perception that is the pain experience in a way that can be quantified by an outside observer (for review, see Lipman J. J., "Pain Measurement," Pain Measurement: Contemporary, Issues in Chronic Pain Management, Ch. 9 (Kluwer Academic Publishers, Boston 1991)). The need for pain measurement methods was recently addressed by both the Social Security Administration and the United States Congress. A report ordered by Congress through the Secretary of Health and Human Services by a Commission on the Evaluation of Pain, recommended that some sort of objective measurement of pain be developed to assist in determining disability (see Fordice, Back Pain in the Workplace: Management of Disability in Nonspecific Conditions-Task Force on Pain in the Workplace, (I.A.S.P. Press, Seattle, 1995); Fields, Core Curriculum for Professional Education in Pain: Task Force on Professional Education, (I.A.S.P. Press, Seattle, 1995); American Pain Society, Principles Of Analgesic Use In the Treatment of
156 Chronic Pain
Acute Pain and Chronic Cancer Pain-a Concise Guide, (American Pain Society, Wash. DC, 1990)). The need for objective pain measurement goes beyond the economics of forensic disability assessment. Objective methods of pain measurement are required for accurate assessment of patient complaint and to assure appropriate treatment. For example, the need to appropriately medicate severe acute and chronic pain and also cancer pain requires an objective method of pain measurement. A corollary need is to avoid inappropriate treatment of pain--or claimed pain--where the possibility of malingering for secondary gain is a possibility. Such "secondary gains" are believed to account for an appreciable portion of chronic pain treatment demand, and forensically include the desire for disability payments, for insurance damage settlements or for other fiduciary incentives. Such secondary gains are not always conscious and may derive from psychological reasons related to the psychosocial set and setting of the patient and their disease. The inappropriate desire for opiate drugs probably accounts for a significant fraction of pain therapy prescription drug demand, yet absent any objective method of establishing the existence of "pain", the physician has no objective standards by which to prohibit such demand, and frequently feels ethically bound to take claims of pain at face value, or risk accusation of ineffective care and inhumane treatment. Web site: http://www.delphion.com/details?pn=US06248079__ •
KIAA0551 polynucleotides and polypeptides use Inventor(s): Bingham; Sharon (Saffron Walden, GB), Case; Patrick (Bristol, GB), Lawson; Sally Neale (Bristol, GB), Newton; Richard Anthony (Bristol, GB), Rausch; Oliver Lars (London, GB), Reith; Alastair David (Barnet, GB), Sanger; Gareth John (Sawbridgeworth, GB) Assignee(s): SmithKline Beecham plc (Brentford, GB) Patent Number: 6,277,979 Date filed: September 10, 1999 Abstract: The use of KIAA0551 polypeptides and polynucleotides in the design of protocols for the treatment of neuropathies, neuropathic pain, inflammatory and chronic pain, neurodegenerative conditions such as Motor Neuron Disease, Parkinson's Disease, Alzheimer's Disease and other dementias, as well as ischaemic damage in neuronal and cardiac tissues, through disease or infectious agents, among others, and diagnostic assays for such conditions. Also disclosed are methods for producing such polypeptides by recombinant techniques. Excerpt(s): This invention relates to new uses for polynucleotides and polypeptides encoded by them, to their use in therapy and in identifying compounds which may be agonists, antagonists and/or inhibitors which are potentially useful in therapy, to production of such polypeptides and polynucleotides, and to the identification of new full-length polynucleotides and polypeptides. In one aspect, the invention relates to new uses of KIAA0551 polynucleotides and polypeptides (Nagase et al., 1998, DNA Res.5, 31-39. Genbank acc. no. AB01123). Such uses include the treatment and/or prophylaxis of neuropathies, neuropathic pain, inflammatory and chronic pain, neurodegenerative conditions such as Motor Neuron Disease, Parkinson's Disease, Alzheimer's Disease and other dementias, as well as neuronal degeneration resulting from ischemic events, including cerebral ischemia after cardiac arrest, stroke and multi-infarct dementia and also after cerebral ischemic events such as those resulting from surgery and/or during childbirth, hereinafter referred to as "the Diseases," amongst others. Thus according to one aspect of the invention there is provided a method of treatment or prophylaxis of a
Patents 157
neurotraumatic disease. Neurotraumatic diseases/events as defined herein include both open or penetrating head trauma, such as caused by surgery, or a closed head trauma injury, such as caused by an injury to the head region. Also included within this definition is ischemic stroke, particularly to the brain area, transient ischemic attacks following coronary by-pass and cognitive decline following other transient ischemic conditions. Web site: http://www.delphion.com/details?pn=US06277979__ •
Method and apparatus for treating chronic pain syndromes, tremor, dementia and related disorders and for inducing electroanesthesia using high frequency, high intensity transcutaneous electrical nerve stimulation Inventor(s): Silverstone; Leon M. (La Jolla, CA) Assignee(s): Synaptic Corporation (Aurora, CO) Patent Number: 6,161,044 Date filed: November 23, 1998 Abstract: Provided herein is a non-invasive method of treating, controlling or preventing medical, psychiatric or neurological disorders, using transcutaneous electrical stimulation. The method employs a plurality of stimulation frequency parameters, ranging from a relatively high frequency, for example about 40,000 Hertz, to a relatively low frequency, for example about 250 Hertz, the entire plurality of frequency parameters being administered at each of a plurality of stimulation intensity levels. In particular, the method involves stimulating at a first highest frequency parameter and a first lowest intensity parameter, incrementally decreasing the stimulation frequency parameter a lowest frequency parameter, increasing the frequency parameter to the highest frequency parameter and increasing the intensity parameter to a next highest intensity parameter, and again stimulating through the plurality of frequency parameters from the highest frequency to the lowest frequency. The method described herein is useful in treating, controlling and/or preventing various disease states and disorders, including without limitation, tremor disorders, such as essential tremor and Parkinson's disease, dementia disorders, such as Alzheimer's disease and painful degenerative disorders, such as reflex sympathetic dystrophy and fibromyalgia. Excerpt(s): The present invention relates to improved methods for the non-invasive treatment of various disease conditions using an improved process of transcutaneous electrical stimulation. In particular, provided herein are improved methods of noninvasively treating symptoms of tremor disorders including essential tremors and tremors associated with Parkinson's Disease; symptoms of dementia disorders including cortical dementia, such as is found in Alzheimer's disease and Pick's disease, subcortical dementia, such as is found in Parkinson's disease, Huntington's chorea and supranuclear palsy, and multi-infarct dementia; and symptoms of painful degenerative disorders, such as fibromyalgia and reflex sympathetic dystrophy by using transcutaneous electrical nerve stimulation programs of variable intensity and variable frequency. Also provided are apparatus for performing such methods. Transcutaneous electrical nerve stimulation (TENS) is a well known medical treatment used primarily for symptomatic relief and management of chronic intractable pain and as an adjunctive treatment in the management of post surgical and post traumatic acute pain. TENS involves the application of electrical pulses to the skin of a patient, which pulses are generally of a low frequency and are intended to affect the nervous system in such a
158 Chronic Pain
way as to suppress the sensation of pain that would indicate acute or chronic injury or otherwise serve as a protective mechanism for the body. Typically, two electrodes are secured to the skin at appropriately selected locations. Mild electrical impulses are then passed into the skin through the electrodes to interact with the nerves lying thereunder. As a symptomatic treatment, TENS has proven to effectively reduce both chronic and acute pain of patients. However, TENS has shown no capacity for curing the causes of pain, rather the electrical energy simply interacts with the nervous system to suppress or relieve pain. The human nervous system essentially serves as a communication system for the body wherein information concerning the state of the body is communicated to the spinal cord (and/or brain) and behavioral instructions are communicated from the brain (and/or spinal cord) to the rest of the body. Thus, there are ascending neural pathways, such as the ascending pain pathways, and descending neural pathways, such as the descending inhibitory pathway (DIP), within the nervous system. Web site: http://www.delphion.com/details?pn=US06161044__ •
Method of treating chronic pain associated with muscle spasms, tendonitis and sciatica Inventor(s): Joseph; William K. (241 Central Park West, #7C, New York, NY 10024) Assignee(s): none reported Patent Number: 6,048,881 Date filed: February 1, 1999 Abstract: The invention is a method of treating chronic pain associated with muscle spasms, tendonitis and sciatica comprising administering to a human patient an effective amount of niacin. Excerpt(s): The present invention relates to a method for treating chronic pain associated with muscle spasms, tendonitis and sciatica by administering to a human patient an effective amount of niacin. Chronic pain associated with conditions such as muscle spasms, tendonitis and sciatica is not only very painful to the individual, but is usually very difficult to treat. Inadequate treatment of chronic pain can be debilitating to humans. Muscle spasms are violent, involuntary contractions of a muscle or a group of muscles. They affect a large segment of the population and are often very painful. The pain resulting from muscle spasms often is chronic, i.e. lasts for one day or even longer. By contrast, the pain associated with leg cramps, which usually radiates from the calf, and can last from a few seconds up to ten minutes. See for example, Weiner et al., JAMA 244:2332-2333 (1980). Web site: http://www.delphion.com/details?pn=US06048881__
Patents 159
•
Method of treating or preventing chronic pain with a highly selective norepinephrine reuptake inhibitor Inventor(s): Ahmed; Saeeduddin (Indinapolis, IN), Birgerson; Lars (Martinsville, NJ), Cetera; Pasquale (Annandale, NJ), Marshall; Robert C. (Mattawan, MI), McArthur; Robert (Kalamazoo, MI), Taylor; Duncan P. (Kalamazoo, MI), Wong; Erik H. F. (Portage, MI) Assignee(s): Pharmacia & UpJohn Company (Kalamazoo, MI) Patent Number: 6,465,458 Date filed: June 22, 2000 Abstract: Methods and compositions for treating humans suffering from, or preventing a human from suffering, a physiological or psychiatric disease, disorder, or a condition where inhibiting reuptake of norepinephrine is a benefit are disclosed. The methods comprise administering the optically pure (S,S) enantiomer of reboxetine. The methods generally include administration of a therapeutic amount of such compositions. Also disclosed are preparations of a medicament from the composition, and uses of the composition in a manufacture of the medicament to treat a human suffering from, or preventing a human from suffering, a physiological or psychiatric disease, disorder, or condition. Excerpt(s): The present invention relates to methods of treating individuals suffering from a variety of conditions wherein inhibiting reuptake of norepinephrine provides a benefit. In particular, the present invention relates to methods of treatment comprising administration of a compound, such as (S,S) reboxetine, to an individual, wherein the compound has a high pharmacological selectivity with respect to norepinephrine reuptake sites compared to serotonin reuptake sites. The present invention also relates to a composition containing the compound and to a preparation of a medicament containing the composition. Many types of depression, mental, behavioral, and neurological disorders originate from disturbances in brain circuits that convey signals using certain monoamine neurotransmitters. Monoamine neurotransmitters include, for example, norepinephrine (noradrenaline), serotonin (5-HT), and dopamine. Lower-thannornal levels of norepinephrine are associated with a variety of symptoms including lack of energy, motivation, and interest in life. Thus, a normal level of norepinephrine is essential to maintaining drive and capacity for reward. These neurotransmitters travel from the terminal of a neuron across a small gap (i.e., the synaptic cleft) and bind to receptor molecules on the surface of a second neuron. This binding elicits intracellular changes that initiate or activate a response or change in the postsynaptic neuron. Inactivation occurs primarily by transport (i.e., reuptake) of the neurotransmitter back into the presynaptic neuron. Abnormality in noradrenergic transmission results in various types of depression, mental, behavioral, and neurological disorders attributed to a variety of symptoms including a lack of energy, motivation, and interest in life. See generally, R. J. Baldessarini, "Drugs and the Treatment of Psychiatric Disorders: Depression and Mania" in Goodman and Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill, NY, NY, pp. 432-439 (1996). Web site: http://www.delphion.com/details?pn=US06465458__
160 Chronic Pain
•
Methods and compositions for treating chronic disorders using optically pure (+)bupropion Inventor(s): McCullough; John R. (Hudson, MA), Rubin; Paul D. (Sudbury, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,458,374 Date filed: January 28, 1999 Abstract: Methods and compositions are disclosed utilizing the optically pure (+)-isomer of bupropion to assist in smoking cessation, for treating smoking and nicotine addiction, and for treating pain, including, but not limited to, chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders such as narcolepsy, chronic fatigue syndrome, fibromyalgia, seasonal affective disorder and premenstrual syndrome, while avoiding adverse affects associated with racemic bupropion. Excerpt(s): This invention relates to methods and pharmaceutical compositions for aiding smoking cessation, treating nicotine addiction, and pain, including chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and l are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06458374__
•
Methods and compositions for treating or preventing sleep disturbances and associated illnesses using very low doses of cyclobenzaprine Inventor(s): Iglehart, III; Iredell W. (Baltimore, MD) Assignee(s): Vela Pharmaceuticals, Inc. (Lawrenceville, NJ) Patent Number: 6,395,788 Date filed: August 11, 2000 Abstract: The present invention relates to methods and compositions comprising a very low dose of cyclobenzaprine or metabolite thereof for preventing and treating sleep disturbances and illnesses manifested with sleep dysfunction including fibromyalgia syndrome, chronic fatigue syndrome, sleep disorders, psychogenic pain disorders or chronic pain syndromes or symptoms thereof. The present invention further relates to methods and compositions for treating sleep disturbances, chronic pain or fatigue in humans suffering from fibromyalgia syndrome, chronic fatigue syndrome, sleep disorders, psychogenic pain disorders, chronic pain syndromes using a very low dose of cyclobenzaprine.
Patents 161
Excerpt(s): The invention relates to methods and compositions comprising very low doses of cyclobenzaprine. The methods and compositions are useful for treating or preventing sleep disturbances. Particularly, the methods and compositions of this invention are useful for treating patients suffering from fibromyalgia syndrome, prolonged fatigue, chronic fatigue, chronic fatigue syndrome, sleep disorders, psychogenic pain disorders, chronic pain syndromes, autoimmune diseases and symptoms thereof. Cyclobenzaprine was first synthesized in 1961. [Villani, F. J., et al., "Dialkylaminoalkyl derivatives of 10,11-dihydro-511-dibenzo a,d cycloheptene and related compounds," J. Med. Pharm. Chem. 5:373-383 (1962)]. Cyclobenzaprine was approved by the U.S. Food and Drug Administration in 1977 for the treatment of acute muscle spasms of local origin. [Katz, W., et al., "Cyclobenzaprine in the Treatment of Acute Muscle Spasm: Review of a Decade of Clinical Experience," Clinical Therapeutics 10:216-228 (1988)]. Cyclobenzaprine is sold as a hydrochloride salt in a 10 mg nonscored tablet under the tradename Flexeril.RTM. (Merck and Co.) or as a generic (Genera, Warner-Chilcott, Duramed, Mylan, Endogenerics, and Watson) for use as a skeletal muscle relaxant. The pharmacokinetics of cyclobenzaprine metabolism have been well studied (e.g., Katz, et al., page 219, supra). The principal side effects of cyclobenzaprine treatment are drowsiness, dry mouth or tongue, dizziness and bad taste. [Katz, W. A., et al.,supra.] Other less common side effects include nausea, tiredness, constipation, blurred vision, nervousness, confusion, abdominal pain and discomfort. Although cyclobenzaprine use has been reported to be associated with the side effects of drowsiness or tiredness, the utility of cyclobenzaprine as an agent for improving the quality of sleep, being a sleep deepener, or treating sleep disturbances when administered using a very low dosage regimen has not been recognized. Web site: http://www.delphion.com/details?pn=US06395788__ •
Methods of treating chronic pain Inventor(s): Caudle; Robert M. (Gainesville, FL), Finegold; Alan A. (Bethesda, MD), Iadarola; Michael J. (Washington, DC), Mannes; Andrew J. (Chevy Chase, MD), Olah; Zoltan (Kensington, MD) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,596,269 Date filed: August 24, 2001 Abstract: This invention pertains to the surprising discovery of novel compositions and methods which selectively treat chronic pain while not significantly affecting basal nociceptive, acute pain, responses. The invention provides for compositions and methods of treating chronic pain by administering beta-endorphin-expressing recombinant expression systems such as adenovirus or adeno-associated virus into a subarachnoid or epidural space. The recombinant virus infects the pia mater connectve tissue cells and the infected cells express the fusion protein, wherein the fusion protein is secreted into the spinal cord parenchymal tissue in an amount effective to treat the chronic pain but not significantly affecting basal nociceptive responses. Excerpt(s): This invention generally pertains to the field of medicine and pain control. In particular, this invention pertains to the surprising discovery that pia mater cells transformed to secrete beta-endorphin will selectively control chronic pain while not significantly affecting basal nociceptive, acute pain, responses. This invention is the surprising discovery of a method of using beta endorphin through genetic engineering
162 Chronic Pain
to treat chronic pain, while at the same time not significantly affecting the ability to react to acutely painful, potentially dangerous, stimuli. As will be explained below, prior to this invention, there was a great amount of academic debate as to whether betaendorphin can be used to treat or control chronic pain. Thus, the discovery of betaendorphin's selective control of chronic pain when secreted by transformed pia mater cells was unpredictable and therapeutically advantageous. Current analgesic therapies often fall short of therapeutic goals and typically have unacceptable side effects. In many chronic pain syndromes, such as those subsequent to neuropathic injury, pain is not well controlled by any currently available method. Furthermore, most chronic pain treatment regimes affect the patient's ability to perceive acute pain, thus blunting or abrogating necessary protective basal nociceptive responses. Web site: http://www.delphion.com/details?pn=US06596269__ •
Methods of using moxonidine to inhibit nociceptive pain Inventor(s): Fairbanks; Carolyn A. (NE. Rochester, MN), Kitto; Kelley F. (Minneapolis, MN), Stone; Laura S. (E. Richmondhill, CA), Wilcox; George L. (N. Golden Valley, MN) Assignee(s): Solvay Pharmaceuticals GmbH (Hannover, DE) Patent Number: 6,117,879 Date filed: September 14, 1998 Abstract: Moxonidine and its physiologically compatible acid-addition salts are used for the treatment and/or prophylaxis of nociceptive pain, and in particular nociceptive acute and chronic pain. Excerpt(s): The present invention is directed to the treatment of nociceptive pain in larger mammals, in particular humans, and to pharmaceutical analgesic formulations. There are a variety of analgesic agents available for pain treatment. The most potent analgesic agents are morphine and related opioid compounds. Since the compounds have the severe drawback of leading to dependence and addiction, other non-opioid analgesic compounds have been developed. Yet so far, all available analgesics possess undesirable side effects, which become particularly apparent upon long term use. It is an object of the invention to develop new analgesic pharmaceutical preparations suitable for the treatment and/or prophylaxis of nociceptive pain in larger mammals, in particular in humans, with an improved activity profile and a favorable therapeutic ratio between antinociceptive activities and other side effects. Web site: http://www.delphion.com/details?pn=US06117879__
•
Non-psychotropic cannabinoids Inventor(s): Fink; George (Tel Aviv, IL), Garzon; Aaron (Rehovot, IL) Assignee(s): Pharmos Corporation (Iselin, IL) Patent Number: 6,610,737 Date filed: November 26, 2002 Abstract: Novel non-psychotropic cannabinoids are disclosed and pharmaceutical compositions comprising these novel compounds are described for preventing neurotoxicity, neuroinflammation, immune or inflammatory disorders comprising as active ingredient the stereospecific (+) enantiomer, having (3S,4S) configuration
Patents 163
of.DELTA.sup.6 tetrahydrocannabinol type compounds. The compositions are particularly effective in alleviating and even preventing neurotoxicity due to acute injuries to the central nervous system, including mechanical trauma, compromised or reduced blood supply as may occur in cardiac arrest or stroke, or poisonings. They are also effective in the treatment of certain inflammatory disorders and chronic degenerative diseases characterized by neuronal loss and chronic pain including neuropathic pain. Excerpt(s): The identification of tetrahydrocannabinol (THC) as the active principle of marijuana (Cannabis sativa) prompted medicinal chemists to develop numerous cannabinoid analogs (reviewed by Barth, in Exp. Opin. Ther. Patents 8:301-313, 1998). These novel compounds were designed to exhibit the beneficial properties of THC without the accompanying psychotropic effects, which limit its therapeutic utility. Potential therapeutic applications have classically included known attributes of marijuana itself such as anti-emesis, analgesia, antiglaucoma and appetite stimulation. More recently recognized roles for non-psychotropic cannabinoids are as neuroprotective and anti-inflammatory agents. Chronic degenerative changes, as well as delayed or secondary neuronal damage following direct injury to the central nervous system (CNS), may result from pathologic changes in the brain's endogenous neurochemical systems. Although the precise mechanisms mediating secondary damage are poorly understood, post-traumatic neurochemical changes may include overactivation of neurotransmitter release or re-uptake, changes in presynaptic or postsynaptic receptor binding, or the pathologic release or synthesis of endogenous factors. The identification and characterization of these factors and of the timing of the neurochemical cascade after CNS injury provides a window of opportunity for treatment with pharmacologic agents that modify synthesis, release, receptor binding, or physiologic activity with subsequent attenuation of neuronal damage and improvement in outcome. A number of studies have suggested that modification of post-injury events through pharmacologic intervention can promote functional recovery in both a variety of animal models and clinical CNS injury. Pharmacologic manipulation of endogenous systems by such diverse pharmacologic agents as anticholinergics, excitatory amino acid antagonists, including specifically NMDA receptor antagonists, endogenous opioid antagonists, catecholamines, serotonin antagonists, modulators of arachidonic acid, antioxidants and free radical scavengers, steroid and lipid peroxidation inhibitors, platelet activating factor antagonists, anion exchange inhibitors, magnesium, gangliosides, and calcium channel antagonists have all been suggested to potentially improve functional outcome after brain injury (McIntosh, J. Neurotrauma 10:215-243, 1993). The pathogenesis of a diverse group of neurological disorders has been linked to excessive activation of excitatory amino acid receptors. These disorders include epilepsy, focal and global ischemia, CNS trauma, and various forms of neurodegeneration including Huntington's chorea, Parkinson's disease and Alzheimer's disease. There has been extensive effort invested in the development of excitatory amino acid receptor antagonists as therapeutic agents (Rogawski, Trends in Pharmacol. Sci. 14:325-331, 1993 and Danbolt, Progress in Neurobiology 65:1-105, 2001). Web site: http://www.delphion.com/details?pn=US06610737__
164 Chronic Pain
•
Process and composition for treating diseases with an oil-in-water emulsion Inventor(s): Exner; Heinrich (Birkenweg 29, 39291 Mockern, DE), Klose; Peter (Pietzpuhler Weg 4,m, 39291 Grabow, DE) Assignee(s): none reported Patent Number: 6,288,026 Date filed: February 23, 2000 Abstract: The invention concerns a process for treating systemic inflammatory response syndrome (SIRS), intensive care requiring conditions, viral diseases, Colitis ulcerosa, Crohn's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, infectious hospital polyresistance conditions of viral and bacterial sources (infections hospitalismus), bronchial asthma, kidney and urethral infections, migraines, rheumatoid arthritis, osteoporosis Sudeck, acute and chronic inflammations, venal and arterial inflammations, acute and chronic exhaustion conditions, tumors, muscle shrinkage diseases, hemorrhoids, chemically induced heart diseases, hypertonia, aging phenomena, acute and chronic pain conditions, spastics, polyneuropathies, prostate neoplasms, hair loss, impotence, neurodermitis, cervical syndrome, tissue traumas, and amyotropic lateral sclerosis (Lou Gehrig's disease), which comprises administering to a patient in need therefor an effective amount of Paravac composition which can suitably comprise in g/ml of 0.01-0.03 polydimethylsiloxane with a polymerization degree of 20400 and a kinematic viscosity of 20-1300 mm.sup.2/s, 0.0-1-0.03 dimethylsulfoxide, 0.030.06 of a hydrophilic emulsifier, and 0.86-0.95 isotonic salt solution, and optionally 0.0001-0.01 Na or Ca salt of EDTA as a chelating agent. Excerpt(s): The present invention relates to a process and composition for the treatment of various diseases with an oil-in-water emulsion. U.S. Pat. No. 5,904,925 describes an oil-in-water emulsion as an incomplete and a complete adjuvant for antigens, which comprises from 0.01% to 30% of a polydimethylsiloxane, from 0.01 to 15% of a complex emulsifier with an HLB of 9016, from 45% to 99% of a pharmaceutically acceptable salt solution, from 0.01% to 10 of dimethylsulfoxide, and from 0.0001% to 1% of a chelating agent (the foregoing incomplete adjuvant of U.S. Pat. No. 5,904,925 being hereinafter referred to as "Paravac"). Peptidoglycans of species-specific Staphylococcus aureus strains and/or of other strains can be added to this incomplete adjuvant composition for immunization, in a concentration of from 0.00001 to 1 mg protein per ml adjuvant, and water soluble natural and/or synthetic polymers in a concentration of from 0.0001 to 10 mg/ml of the adjuvant. The patent also discloses the use of that adjuvant against a variety of diseases, and this application is a further development and a completion of that earlier invention. Thus any reference herein to a "Paravac" emulsion or composition, other than in the specific examples, is intended to encompass both the incomplete and the complete adjuvant compositions of U.S. Pat. No. 5,904,925. That earlier invention provided adjuvancies which by combination with immunizing antigens or in combination with peptidoglycans into a pharmaceutically acceptable formulation will stimulate the defense mechanisms of the body to such an extent that in addition to the active immune prophylaxis also weak antigens produce a general and specific immunotherapy. Good results are obtained with this adjuvant in immunotherapy. It is a drawback that the preparation of the complete adjuvant, or the adding of proteins have relatively substantial requirements. The danger of an anaphylactic reaction in the host is a pathophysiological drawback of the complete adjuvant in the case of repeated use. Web site: http://www.delphion.com/details?pn=US06288026__
Patents 165
•
Substituted quinazolines and analogs and use thereof Inventor(s): Cai; Sui X. (San Diego, CA), Fick; David B. (Newport Beach, CA), Field; George (Danville, CA), Lan; Nancy C. (S. Pasadena, CA), Upasani; Ravi (San Jose, CA), Wang; Yan (San Diego, CA) Assignee(s): Euro-Celtique S.A. (Luxembourg, LU) Patent Number: 6,465,472 Date filed: September 1, 2000 Abstract: The invention relates to novel quinazolines and heterocycles which are antagonists or positive modulators of AMPA receptors, and the use thereof for treating, preventing or ameliorating neuronal loss associated with stroke, global and focal ischemia, CNS trauma, hypoglycemia and surgery, as well as treating or ameliorating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Down's syndrome, treating, preventing or ameliorating the adverse consequences of the overstimulation of the excitatory amino acids, treating, preventing or ameliorating anxiety, psychosis, convulsions, chronic pain, glaucoma, retinitis, urinary incontinence, muscular spasm and inducing anesthesia, as well as for treating or ameliorating the adverse consequences of excitatory amino acid deficiency such as schizophrenia, myoclonus. Alzheimer's disease and malnutrition and neural maldevelopment, and as cognition and learning enhancers. Excerpt(s): This invention is in the field of medicinal chemistry. In particular, the invention is related to novel substituted quinazolines and analogs thereof. These compounds are antagonists of.alpha.-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) ionotropic receptors. Certain of these compounds are positive modulators of AMPA receptors. The invention also is directed to the use of novel substituted quinazolines and analogs thereof for the treatment of neuronal damage following global and focal ischemia, and for the treatment or prevention of neurodegenerative conditions as anticonlvulsants, as cognitive enhancers, and for the treatment of schizophrenia, Parkinson's disease and myoclonus. The compounds of the invention are also useful for treatment or prevention of pain, including acute and chronic pain. The invention also is directed to a process for the preparation of the substituted quinazolines and analogs thereof. Excitatory amino acid receptors are classified into two general types. Receptors that are directly coupled to the opening of cation channels in the cell membrane of the neurons are termed "ionotropic." This type of receptor has been subdivided into at least three subtypes, which are defined by the depolarizing actions of the selective agonist Nmethyl-D-aspartate (NMDA),.alpha.-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainic acid (KA). The second general type is the G-protein or second messenger-linked "metabotropic" excitatory amino acid receptor. This second type, when activated by the agonists quisqualate, ibotenate, or trans-1-aminocyclopentane1,3-dicarboxylic acid, leads to enhanced phosphoinositide hydrolysis in the postsynaptic cell. Both types of receptors appear not only to mediate normal synaptic connections during development, but also change in the efficiency of synaptic transmission throughout life. (Schoepp, Bockaert, and Sladeczek, Trends Pharm. Sci. 11:508 (1990); McDonald and Johnson, Brain Res. Rev. 15:41 (1990)). The excessive or inappropriate stimulation of excitatory amino acid receptors leads to neuronal cell damage or loss by a mechanism known as excitotoxicity. The medical consequences of such neuronal degeneration makes the abatement of these degenerative neurological processes an important therapeutic goal. (See U.S. Pat. No. 5,284,957). Antagonists of the AMPA receptor are considered useful in treating, preventing and ameliorating a number of neurologic disorders which are due to overstimulation by the excitatory amino acids.
166 Chronic Pain
These include acute neurologic disorders such as domoic acid poisoning; cerebral ischemia, global ischemia associated with cardiac arrest; stroke; spinal cord trauma; hypoxia; anoxia; poisoning be carbon monoxide, manganese or cyanide; hypoglycemia; mechanical trauma to the nervous system; epileptic seizures; and chronic neurologic disorders such as Huntington's disease, neuronal injury associated with HIV and AIDS, AIDS dementia, neuropathic pain syndrome, olivopontocerebral atrophy, Parkinson's disease, amyotrophic lateral sclerosis, mitochondrial abnormalities, Alzheimer's disease, hepatic encephalopathy, Tourette's syndrome, drug addiction and urinary incontinence (see Lipton and Rosenberg, N. Engl. J. Med. 330: 613-622 (1994)) and treatment or amelioration of a number of chronic neurologic disorders such as schizophrenia. AMPA receptor antagonists are also useful in treating, preventing and ameliorating acute and chronic pain, pain associated with post-therapeutic neurolgia, insterstital cystitis, osteoarthritis, spinal cord injury, cancer and diabetic neuropathy. Web site: http://www.delphion.com/details?pn=US06465472__ •
Transplantation of neural cells for the treatment of chronic pain or spasticity Inventor(s): Dinsmore; Jonathan (Brookline, MA), Siegan; Julie (Boston, MA) Assignee(s): Diacrin, Inc. (Charlestown, MA) Patent Number: 6,444,205 Date filed: September 30, 1998 Abstract: Methods for using neural cells to treat chronic pain and/or spasticity are described. The neural cells can be derived from any mammal, and are preferably human or porcine in origin. The neural cells preferably are serotonergic cells or are gammaaminobutryic acid (GABA)--producing cells. Neural cells can be obtained from adult, juvenile, embryonic or fetal donors. Neural cells can be modified to be suitable for transplantation into a subject. For example, the neural cells can be modified such that an antigen (e.g., an MHC class I antigen) on the cell surface which is capable of stimulating an immune response against the cell in a subject is altered (e.g., by contact with an antiMHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cell when introduced into the subject or can be genetically modified to produce a factor. In one embodiment, the neural cells are obtained from a pig which is essentially free from organisms or substances which are capable of transmitting infection or disease to the recipient subject. The neural cells of the present invention can be used to treat chronic pain and/or spasticity by delivering the cells into the spinal cord of a subject. Excerpt(s): Sensory nerve fibers originate from neurons in the posterior root ganglia and enter the spinal cord through the posterior nerve root. The anterior and posterior nerve roots unite distal to the cord to form a mixed spinal nerve which further combines in the cervical and lumbar areas to form the cervical, brachial, and lumbosacral plexuses. Each plexus gives rise to a number of individual mixed nerves, which are distributed to the periphery to supply muscle, skin, and blood vessels. Small myelinated axons carry sensations for pain and temperature, while so-called unmyelinated axons, which are invested by Schwann cell membranes without sheath formation, carry pain and deeper ill-defined sensation. (Gilroy. 1990. Basic Neurology. Second Edition. (McGraw Hill, Inc.) p. 352). Under normal conditions, signals (induced, for example, by thermal, mechanical, and chemical stimuli) activate nerve fiber nociceptors and these signals are conducted to the spinal cord. The signals are then transmitted to the thalamus and cerebral cortex resulting in pain awareness (Dray and Urban. 1996. Annu. Rev. Pharmacol. Toxicol. 36:253). Ordinarily, nociceptive pain can be beneficial in that it can
Patents 167
serve as a warning mechanism to indicate potential tissue damage. In contrast, chronic pain conditions can develop in which a stimulus and the pain response are not related; i.e., the pain does not serve a physiologically protective purpose. It has been estimated that 10-20% of the adult population suffer from chronic pain. (Dray and Urban. 1996. Annu. Rev. Pharmacol. Toxicol. 36:253). Chronic pain differs from acute pain in that it can be incessant. Chronic pathologic lesions, neurodgeneration processes, or prolonged dysfunction of parts of the peripheral or central nervous system can cause chronic pain. Chronic pain, for example, can be described as pain which persists beyond the normal healing time for a disease or injury, pain related to chronic degenerative disease or a persistent neurologic condition, pain that emerges or persists (even recurring for months to years without an identifiable cause, or as pain associated with cancer (Markinson. 1996. Am. Journal of Medicine. 101: 1A-6S). Exemplary chronic pain conditions can be grouped into the following exemplary groups: headache or migraine, arthritis (rheumatoid or osteogenic), back pain, musculoskeletal, neurologic or orofacial, cardiac or visceral. Web site: http://www.delphion.com/details?pn=US06444205__ •
Tricyclic antidepressants and their analogues as long-acting local anesthetics and analgesics Inventor(s): Gerner; Peter (Weston, MA), Wang; Ging Kuo (Westwood, MA) Assignee(s): The Brigham and Women's Hospital Inc. (Boston, MA) Patent Number: 6,545,057 Date filed: September 26, 2001 Abstract: Methods and compositions of tricyclic antidepressants for inducing local longlasting anesthesia and analgesia are provided. The methods and compositions are useful for alleviating acute and chronic pain, particularly useful for treating a localized pain. Excerpt(s): This invention relates to the use of the tricyclic antidepressants to produce local long-acting relief of different varieties of pain. To provide a better understanding of the invention it is necessary to distinguish between the two terms analgesia and anesthesia. Analgesia is defined as a condition in which nociceptive stimuli are sensed but are not interpreted as pain. Anesthesia is a state characterized by total loss of sensation, the result of pharmacologic depression of nerve function. Thus, analgesia does not produce anesthesia whereas anesthesia produces analgesia. In general, pain is associated with a known tissue pathology (e.g., cancer pain, arthritic pain), inflammation, or injury to a body tissue (e.g., surgery). Neuropathic pain is thought to be a consequence of damage to peripheral nerves or to regions of the central nervous system. Neuropathic pain can present as an acute pain but frequently occurs as a form of chronic pain. Web site: http://www.delphion.com/details?pn=US06545057__
168 Chronic Pain
•
Triple drug therapy for the treatment and prevention of acute or chronic pain Inventor(s): Ockert; David M. (145 E. 32nd St., Sixth Floor, New York, NY 10016) Assignee(s): none reported Patent Number: 6,417,184 Date filed: August 17, 2001 Abstract: A triple drug therapy, pharmaceutical kit, composition, and method of treatment regimen utilized as a combination of effective amounts of an anxiolytic agent, centrally acting alpha antiadrenergic agent, and central nervous system stimulant for the reduction or prevention of dizziness, drowsiness, depression, delirium, lethargy, mania, orthostatic hypotension, restlessness, weakness in the extremities, and difficulty in being mobile negative side effects caused by therapeutic agents utilized in the treatment of acute and chronic pain syndromes. Excerpt(s): The present invention relates to the treatment and prevention of acute or chronic pain syndromes. Pain sensation is complex and variable. Experiences considered painful by one subject may not be equally painful to another and may vary in the same subject depending on the circumstances presented. In addition, subjective experiences, i.e. "phantom limb pain" make it clear that there is a strong psychological component to pain. Wingard et al., Human Pharmacology: Molecular to Clinical, Mosby-Year Book, Inc., 1991, p. 383. Several groups of compounds are used to relieve pain, depending on the severity and duration of the pain sensation, and on the nature of the painful stimulus. Drugs used to relieve mild, moderate or severe pain without causing unconsciousness are generally called analgesics. Mild analgesics that are termed non-narcotic agents include aspirin, acetaminophen and non-steroidal antiinflammatory drugs. Should non-narcotic based agents prove ineffective, narcotic/opioid analgesic agents such as morphine, codeine, meperidine, and the like are used to treat more severe acute or chronic forms of pain. Ibid., pp. 383, 391-92. Web site: http://www.delphion.com/details?pn=US06417184__
•
Use of purine receptor agonists to alleviate or normalize physiopathologically excited sensory nerve function Inventor(s): Fukunaga; Atsuo F. (5411 Littlebow Rd., Rancho Palos Verdes, CA 90275) Assignee(s): none reported Patent Number: 6,180,616 Date filed: December 7, 1999 Abstract: A method for the alleviation or normalization (i.e., treatment) of physiopathologically excited sensory nerve function (i.e., pain) comprising the administration of a purine receptor agonist in an effective amount to a mammal other than a rodent. In a preferred embodiment, pain is treated in a human by the administration of an effective amount of a purine receptor agonist. In an alternative embodiment, an adenosine compound, such as but not limited to adenosine or adenosine triphosphate, is administered in an effective amount to a human to treat surgical pain, chronic pain, and/or traumatic pain. Human patients receiving a continuous infusion of an adenosine compound during surgery reported a profound analgesic effect after surgery.
Patents 169
Excerpt(s): This invention relates to a method of using adenosine compounds to induce anesthesia, sedation, analgesia, hypothermia, and to ameliorate stress. A patient is protected from the pain and stress of surgery and similar procedures by anesthesia which allows the maintenance of physiological homeostasis. Adenosine has a variety of extracellular effects. It is known to have potent vasodilating, blood pressure lowering (hypotensive) and shock-inducing effects, but has never been demonstrated to have anesthetic activity when used clinically. Furthermore, the conventional wisdom is that neither adenosine nor adenosine triphosphate (hereinafter ATP), an adenine nucleotide, circulating in the blood, will cross the blood brain barrier. Therefore, despite analgesic and sedative effects suggested by previous studies in laboratory experiments, neither adenosine nor ATP had ever been thought to be suitable as anesthetics. A major problem with prior studies is that they were performed under such poorly controlled conditions that the vital signs: circulatory, such as blood pressure, heart rate and respiratory functions were not measured. Because data on the behavior of these parameters are essential in determining therapeutic efficacy, these studies failed to teach whether such potential analgesic and sedative effects were caused by the profound effects of these compounds on cardiovascular function, namely: hypotension, coma, bradycardia, or shock. Failure to determine the vital signs, and to isolate the analgesic properties from the coma or shock, which may be produced by potent hypotensive effects of adenosine, render these reports fatally flawed as teaching analgesia or sedation caused by adenosine. Consequently, previous studies do not evaluate usage for treatment purposes of these agents. Based on previous reports, such effects (analgesia, sedation) could not possibly have been translated to clinical applicability. Web site: http://www.delphion.com/details?pn=US06180616__
Patent Applications on Chronic Pain As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to chronic pain: •
4-Substituted piperidine analogs and their use as subtype selective NMDA receptor, antagonists Inventor(s): Bigge, Christopher F.; (Ann Arbor, MI), Cai, Sui Xiong; (Foothill, CA), Keana, John F.W.; (Eugene, OR), Lan, Nancy F.; (South Pasadena, CA), Weber, Eckard; (Laguna Beach, CA), Woodward, Richard; (Aliso Viejo, CA), Wright, Jonathan; (Ann Arbor, MI), Zhou, Zhang-Lin; (Irvine, CA) Correspondence: Fitzpatrick Cella Harper & Scinto; 30 Rockefeller Plaza; New York; NY; 10112; US Patent Application Number: 20030105133 Date filed: July 29, 2002 Abstract: Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs as selectively active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma,
10
This has been a common practice outside the United States prior to December 2000.
170 Chronic Pain
hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, glaucoma, CMV retinitis, chronic pain, opioid tolerance or withdrawals, or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described. Also described are novel methods for preparing 4-substituted piperidine analogs and novel intermediates of the 4-substituted piperidine analogs. Excerpt(s): This invention is related to 4-substituted piperidine analogs, including hydroxypiperidine and tetrahydropyridine analogs, as well as novel intermediates of the 4-substituted analogs. The analogs are selectively active as antagonists of N-methylD-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 4substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neuro-degenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Ar.sup.1 and Ar.sup.2 are each independently substituted or unsubstituted aryl, a heteroaromatic ring, or a heteroaromatic bicylic ring. The tetrahydropyridines and hydroxypiperidines of this reference are indicated to be useful as central nervous system agents, particularly as dopaminergic, antipsychotic and antihypertensive agents, and for treating central nervous system disorders such as Parkinson Disease, Huntington Disease and depression. The particular 4-substituted piperidines, including the 4-hydroxypiperdines and tetrahydropyridines of this invention are not exemplified. In addition, there is no disclosure or suggestion of treating disorders with selective NMDA receptor subtype antagonists and the advantages of such treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Anellated dihydropyridines for the treatment of chronic pain Inventor(s): Arndts, Dietrich; (Appenheim, DE), Blech, Stefan Matthias; (Warthausen, DE), Draheim, Henning; (Ingelheim, DE), Gaida, Wolfram; (Ingelheim, DE), Klinder, Klaus; (Ingelheim, DE), Loesel, Walter; (Mainz, DE) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P. O. Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20030114480 Date filed: September 11, 2002 Abstract: The invention relates to the use of anellated dihydropyridines according to the following formula I, and the salts thereof with physiologically acceptable acids, for the treatment of chronic pain, wherein A is benzo or thieno and Z, R.sup.1, R.sup.2, R.sup.3,
Patents 171
R.sup.4, R.sup.5 and R.sup.6 are defined as in the specification: 1The inventions also relates to novel compounds of formula I and pharmaceutical compositions thereof. Excerpt(s): This application is a division of U.S. application Ser. No. 09/908,962, filed Jul. 19, 2001, which claims benefit of U.S. Provisional Application Serial No. 60/223,871, filed on Aug. 8, 2000 and both applications are incorporated herein by reference in their entirety. The invention relates to the use of anellated dihydropyridines and the salts thereof with physiologically acceptable acids for preparing agents for the treatment of chronic pain. wherein ZR.sup.6 denotes para-phenoxy. There is no reference therein to the treatment of chronic pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Antidepressants and their analogues as long-acting local anesthetics and analgesics Inventor(s): Gerner, Peter; (Weston, MA), Verrecchia, Donald K.; (Winchester, MA), Wang, Ging Kuo; (Westwood, MA) Correspondence: Edward R. Gates, ESQ.; Chantal Morgan D'apuzzo, PH.D.; Wolf, Greenfield & Sacks, P.C.; 600 Atlantic Avenue; Boston; MA; 02210; US Patent Application Number: 20030096805 Date filed: April 4, 2002 Abstract: Methods and compositions of antidepressants and analogs thereof for inducing local long-lasting anesthesia and analgesia are provided. The methods and compositions are useful for alleviating acute and chronic pain, particularly useful for treating a localized pain. Excerpt(s): This application claims priority to and is a continuation in part of co-pending U.S. application Ser. No. 09/965,138 filed on Sep. 26, 2001, which claims priority to U.S. application Serial No. 60/235,432 filed on Sep. 26, 2000. This invention relates to the use of antidepressants and analogs thereof to produce local long-acting relief of different varieties of pain. To provide a better understanding of the invention it is necessary to distinguish between the two terms analgesia and anesthesia. Analgesia is defined as a condition in which nociceptive stimuli are sensed but are not interpreted as pain. Anesthesia is a state characterized by total loss of sensation, the result of pharmacologic depression of nerve function. Thus, analgesia does not produce anesthesia whereas anesthesia produces analgesia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Aryl substituted pyridines and their use Inventor(s): Goehring, R. Richard; (Pipersville, PA), Shao, Bin; (Richboro, PA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W., Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20030073724 Date filed: September 6, 2002 Abstract: This invention relates to aryl substituted pyridines of Formula I: 1or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein Ar and R.sub.1R.sub.4 are set in the specification. The invention is also directed to the use of
172 Chronic Pain
compounds of Formula I for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, including diabetic neuropathy, as antitinnitus agents, as anticonvulsants, and as antimanic depressants, as local anesthetics, and as antiarrhythmics. Excerpt(s): This application claims the priority benefit under 35 U.S.C.sctn.119(e) of U.S. Provisional Application No. 60/317,455, filed Sep. 7, 2001, the entirety of which is incorporated by reference herein. This invention is in the field of medicinal chemistry. In particular, the invention relates to novel aryl substituted pyridines and the discovery that these compounds act as blockers of sodium (Na.sup.+) channels. Several classes of therapeutically useful drugs, including local anesthetics such as lidocaine and bupivacaine, antiarrhythmics such as propafenone and amioclarone, and anticonvulsants such as lamotrigine, phenytoin and carbamazepine, have been shown to share a common mechanism of action by blocking or modulating Na.sup.+ channel activity (Catterall, W. A., Trends Pharmacol. Sci. 8:57-65 (1987)). Each of these agents is believed to act by interfering with the rapid influx of Na.sup.+ ions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Chronic pain patient medical resources forecaster Inventor(s): Carlson, Angeline M.; (Eden Prairie, MN), Goetzke, Gary A.; (St. Paul, MN), Jackson, Jack M.; (Minneapolis, MN), Johns, Thomas N.P.; (Minneapolis, MN), Reid, Malcolm E.; (St. Paul, MN) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030097185 Date filed: April 27, 2001 Abstract: The medical resource for chronic pain patients are forecasted using a method or computer software product to improve accuracy in forecasting medical resources, decrease the time required to forecast medical resources, and many other benefits. Desired patient indicia including direct medical indicia, indirect medical indicia, and non-medical indicia are selected to serve as independent variables. At least one chronic pain indication is selected to serve as a dependent variable. A chronic pain forecasting model is created using the patient indicia and the chronic pain indication. The chronic pain forecasting model is applied to a chronic pain patient indicia to create a patient forecast. Many different embodiments of the chronic pain patient dynamic medical resources forecaster method and software product are possible. Excerpt(s): This application claims the benefit of provisional application U.S. Serial No. 60/258,556 filed on Dec. 29, 2000 entitled "Disease Management System And Methods" by Goetzke et al. This application is also related to the following co-pending applications entitled "Chronic Pain Patient Identification System" by inventors Goetzke et al. (attorney docket number P9581.00); "Chronic Pain Patient Risk Stratification System" by inventors Goetzke et al. (attorney docket number P9640.00); "Chronic Pain Patient Diagnosis System" by inventors Goetzke et al. (attorney docket number P9641.00); "Chronic Pain Patient Care Plan" by inventors Goetzke et al. (attorney docket number P9643.00) which are not admitted as prior art with respect to the present invention by its mention in this cross reference section. This disclosure relates to a
Patents 173
medical information system and more specifically to a chronic pain patient medical resources forecaster computer program and method. Although medical treatment of acute injuries and illnesses have improved significantly over the past few decades, chronic disease remains by far the greatest cause of mortality, diminished quality of life, and increased healthcare expenditures. Approximately 80% of healthcare costs are spent on the treatment of chronic disease, much of it on unnecessary hospitalizations, inappropriate medical interventions, and poor overall coordination of care. This is true because chronic diseases are commonly treated but quite frequently not appropriately managed. The bulk of these expenses are spent on cardiovascular disease, cancer, diabetes, AIDS, orthopedic and spinal disease, arthritis, and the full range of neurological diseases. In countries with an aging population, the prevalence of chronic disease will increase dramatically, further accentuating the need for better chronic care. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Clostridial toxin derivatives able to modify peripheral sensory afferent functions Inventor(s): Duggan, Michael John; (London, GB), Foster, Keith Alan; (Wiltshire, GB), Shone, Clifford Charles; (Wiltshire, GB) Correspondence: Stephen A. Bent; Foley & Lardner; Washington Harbour; 3000 K Street, N.W., Suite 500; Washington; DC; 20007-5143; US Patent Application Number: 20030049264 Date filed: May 20, 2002 Abstract: The invention relates to an agent specific for peripheral sensory afferents. The agent may inhibit the transmission of signals between a primary sensory afferent and a projection neutron by controlling the release of at least one neurotransmitter or neuromodulator from the primary sensory afferent. The agent may be used in or as a pharmaceutical for the treatment of pain, particularly chronic pain. Excerpt(s): This invention relates to a novel agent that is able to modify peripheral afferent function. The agent may inhibit neurotransmitter release from discrete populations of neurons, and thereby reduce, or preferably prevent, the transmission of afferent pain signals from peripheral to central pain fibres. The agent may be used in or as a pharmaceutical for the treatment of pain, particularly chronic pain. The sense of touch has traditionally been regarded as one of the five classical senses, but in reality it is highly complex, transducing a number of different sensations. These sensations are detected in the periphery by a variety of specialised nerve endings and associated structures. Some of these are specific for mechanical stimuli of various sorts such as touch, pressure, vibration, and the deformation of hairs or whiskers. Another class of nerves is able to detect temperatures, with different fibres being activated by heat and cold. A further population of nerve endings is not normally excited by mild stimuli, but by strong stimuli only. Sensory nerves of this category often respond to more than one stimulus, and are known as high-threshold polymodal fibres. They may be used to sense potentially damaging situations or objects. The polymodal fibres also transduce chemical signals such as the "burning" sensation evoked by acid. Thus, the sense of touch can transmit a very detailed description of objects and serve to both inform and warn of events. The transduction of sensory signals from the periphery to sensation itself is achieved by a multi-neuronal pathway and the information processing centres of the brain. The first nerve cells of the pathway involved in the transmission of sensory stimuli are called primary sensory afferents. The cell bodies for the primary sensory afferents from the head and some of the internal organs reside in various of the ganglia
174 Chronic Pain
associated with the cranial nerves, particularly the trigeminal nuclei and the nucleus of the solitary tract. The cell bodies for the primary sensory afferents for the remainder of the body lie in the dorsal root ganglia of the spinal column. The primary sensory afferents and their processes have been classified histologically; the cell bodies fall into two classes: A-type are large (60-120.mu.m in diameter) while B-type are smaller (1430.mu.m) and more numerous. Similarly the processes fall into two categories: C-fibres lack the myelin sheath that A-fibres possess. A-fibres can be further sub-divided into A.beta.-fibres, that are large diameter with well developed myelin, and A.delta.-fibres, that are thinner with less well developed myelin. It is generally believed that A.beta.fibres arise from A-type cell bodies and that A.delta.and C-fibres arise from B-type cell bodies. These classifications can be further extended and subdivided by studying the selective expression of a range of molecular markers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and medical device for transdermal delivery of a drug and methods of making and using same Inventor(s): Brown, Teletha A.; (Piscataway, NJ), Hunt, Brian; (Harriman, NY), Malik, Vinod; (Toms River, NJ), Osborne, James; (Princeton Junction, NJ), Rudella, Michael; (Cedar Knolls, NJ) Correspondence: Allen Bloom; C/o Dechert; Princeton Pike Corporation Center; P.O. Box 5218; Princeton; NJ; 08543-5218; US Patent Application Number: 20030060479 Date filed: August 15, 2002 Abstract: The invention relates to transdermal delivery patches comprising a drugcontaining drug reservoir wherein the drug reservoir comprises a plasticizer composition selected to adjust the rate of drug flux out of the transdermal delivery patch device. The invention also specifically relates to methods of producing the transdermal delivery patches of the invention, the methods comprising the use of an alcohol drug dispersing agent. The invention further specifically relates to methods of treating acute and chronic pain and methods of inducing and maintaining analgesia with the transdermal delivery patches of the invention. Excerpt(s): This Application claims benefit to U.S. Provisional Application No. 60/313,055, filed on Aug. 17, 2001, the disclosure of which is incorporated herein by reference in its entirety as if fully set forth herein. The present invention relates to medical devices comprising a solid drug reservoir formulation for percutaneous administration of a drug, to methods of treating medical conditions with the same, and to methods of preparing such devices. More specifically, the invention relates to transdermal delivery patches comprising a drug reservoir; wherein the drug reservoir comprises a plasticizer composition selected to adjust the rate of flux of the drug out of the transdermal delivery patch device and wherein the drug is selected from the group consisting of fentanyl, oxymorphone, oxycodone, hydromorphone, morphine, buprenorphine and analgesically effective derivatives thereof, preferably fentanyl. The invention also specifically relates to methods of producing the transdermal delivery patches of the invention, the methods comprising the use of an alcohol drug dispersing agent to disperse the drug in a preparative solution. The invention further specifically relates to methods of treating acute and chronic pain and methods of inducing and maintaining analgesia with the transdermal delivery patches of the invention. Fentanyl and its analgesically effective derivatives (hereafter referred to as "derivatives") such as
Patents 175
sufentanyl, carfentanyl, lofentanyl and alfentanyl have long been known as anesthetics and analgesics. Fentanyl and its derivatives are potent, rapidly metabolized drugs having a relatively narrow therapeutic index which produce extremely undesirable side effects on overdosage, most notably respiratory depression. Fentanyl-containing compositions are also relatively expensive and have a high potential for abuse. Skin is known to contain fentanyl binding sites that must be saturated before any significant absorption into the bloodstream occurs. Accordingly, when fentanyl is administered transdermally, the rate of administration to an area of a subject's skin should be controlled in a reproducible fashion to produce an initial dose of fentanyl that rapidly saturates fentanyl skin binding sites, and then provide a more steady medically appropriate flux of fentanyl through an area of skin throughout an administration period. Preferred administration periods for fentanyl patch transdermal delivery devices are about 1-7 days. Thus, medical devices for transdermal administration of fentanyl should provide for a rate-controlled release of fentanyl according to a medically appropriate dose rate during an administration period. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods of use for extracts of Rutaceae plants Inventor(s): Chambliss, Walter; (Memphis, TN), Stogniew, Martin; (Blue Bell, PA) Correspondence: William J. Brucker, ESQ.; Stetina Brunda Garred & Brucker; Suite 250; 75 Enterprise; Aliso Viejo; CA; 92656; US Patent Application Number: 20030215531 Date filed: March 20, 2003 Abstract: The invention relates to compositions and methods for preventing, treating, or managing anxiety, pain, chronic pain, depression, and disorders such as premenstrual syndrome comprising the administration of a prophylactically and therapeutically effective amount of Rutaceae plant or extracts thereof to a mammal in need of such therapy. In a preferred embodiment, the mammal is human and the extracts are substantially free of the compounds obacunone or limonin. The invention also relates to compositions and methods for preventing, treating, or managing separation anxiety in domestic animals comprising the administration of a prophylactically and therapeutically effective amount of Rutaceae plant or extracts thereof to an animal in need of such therapy. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/235,920 filed Sep. 28, 2000, which is incorporated herein by reference. The present invention relates to novel methods and compositions for the treatment, prevention, or management of anxiety, pain, chronic pain, depression, disorders such as premenstrual syndrome, weight loss, cold, appetite loss, sleeplessness, and fatigue. The methods and compositions utilize plants, portions thereof or extracts therefrom belonging to the Rutaceae family, preferably the extract is substantially free of the compounds obacunone or limonin. In addition, the methods and compositions utilize mixtures of specific small molecules extracted from the Rutaceae plant, such as, but not limited to, berberine, phellodendrine, and magnoflorine. The unique compositions of the invention may also comprise various amounts of the Rutaceae plant, plant extract, plant extracts combined with different amounts of biologically active small molecules or other therapeutic agents. These compositions are particularly useful for the treatment of anxiety, pain, chronic pain, depression, premenstrual syndrome, weight loss, cold, appetite loss, sleeplessness and fatigue in humans. The invention also encompasses
176 Chronic Pain
various modes of administration of the therapeutic extracts or other compositions of the invention. Finally, the compositions of the invention can be formulated for veterinary use since they are also useful for the treatment of separation anxiety in domestic animals. The recent growth in sales of natural products labeled as dietary supplements in the United States has renewed scientific interest in the study of the prophylactic and therapeutic effects of multi-component botanical products. Unlike single entity pharmaceutical products, botanical products comprise a large number of diverse chemical constituents that often act synergistically to exert a desired biological effect. The type of extraction process utilized and the manner in which the formulation is standardized have dramatic effects on the pharmacological activity of the final product. The development of new botanical products requires multidisciplinary effort consisting of expertise in ethnobotany, natural product chemistry, analytical chemistry, pharmacology, and natural product extraction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions comprising sibutramine phosphodiesterase inhibitors
metabolites
in
combination
with
Inventor(s): Fang, Qun K.; (Wellesley, MA), Jerussi, Thomas P.; (Framingham, MA), Senanayake, Chrisantha H.; (Shrewsbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20030096792 Date filed: October 23, 2002 Abstract: Methods are disclosed for the treatment and prevention of disorders and conditions such as, but are not limited to: eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence.Pharmaceutical compositions and dosage forms are also disclosed which comprise a racemic or optically pure sibutramine metabolite and an optional additional pharmacologically active compound. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/662,135, filed Sep. 14, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/372,158, filed Aug. 11, 1999, both of which are incorporated herein by reference in their entireties. The invention relates to methods of using and compositions comprising dopamine reuptake inhibitors such as racemic and optically pure metabolites of sibutramine, optionally in combination with other pharmacologically active compounds. Sibutramine, chemically named [N-1-[1-(4-chlorophenyl)cyclobutyl]3- -methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 177
•
Compounds and method of treatment having agonist-like activity selective at alpha 2B or 2B/2C adrenergic receptors Inventor(s): Burke, James A.; (Santa Ana, CA), Chow, Ken; (Newport Coast, CA), Garst, Michael E.; (Newport Beach, CA), Gil, Daniel W.; (Corona Del Mar, CA), Harcourt, Dale A.; (Irvine, CA), Wheeler, Larry A.; (Irvine, CA) Correspondence: Carlos A. Fisher; Allergan, INC.; T2-2e; 2525 Dupont Drive; Irvine; CA; 92623; US Patent Application Number: 20030023098 Date filed: March 21, 2001 Abstract: Methods and compounds for the treatment of conditions including pain, particularly chronic pain, glaucoma or elevated intraocular pressure with reduced cardiovascular or sedative side effects. Also included are methods of making and using such compounds. Excerpt(s): This application is a continuation in part of application Ser. No. 09/329,752, filed Jun. 10, 1999, which was a continuation in part of application Ser. No. 09/205,597, filed Dec. 4, 1998, now abandoned, which was a continuation in part of application Ser. No. 08/985,347, filed Dec. 4, 1997, now abandoned. The present invention is directed to a method of treating pain, particularly chronic pain, glaucoma or elevated intraocular pressure and other diseases with substantially reduced cardiovascular or sedative side effects by administering to mammals including humans, compounds which are selective agonists of the.alpha.2B alone or.alpha.2B and.alpha.2C adrenergic receptor subtypes and which lack substantial activity at the a2A receptor subtype. The present invention is also directed to novel compounds and pharmaceutical compositions adapted for administering said compounds to mammals, including humans. Compounds which have adrenergic activity are well known in the art, and are described in numerous United States and foreign patents and in scientific publications. It is generally known and accepted in the art that adrenergic activity is useful for treating animals of the mammalian species, including humans, for curing or alleviating the symptoms and conditions of numerous diseases and conditions. In other words, it is generally accepted in the art that pharmaceutical compositions having an adrenergic compound or compounds as the active ingredient are useful for treating glaucoma, chronic pain, nasal congestion, high blood pressure, congestive heart failure and inducing anesthesia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Cyclopropylindole derivatives as selective serotonin reuptake inhibitors Inventor(s): Catt, John D.; (Newburgh, IN), Denhart, Derek John; (Wallingford, CT), Deskus, Jeffrey A.; (Marlborough, CT), Ditta, Jonathan L.; (Middletown, CT), Epperson, James R.; (Cromwell, CT), Higgins, Mendi A.; (Middletown, CT), King, Dalton; (Hamden, CT), Marcin, Lawrence R.; (Bethany, CT), Mattson, Ronald J.; (Meriden, CT) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030073849 Date filed: March 5, 2002 Abstract: The present invention relates to compounds of Formula (I) and pharmaceutically acceptable salts or solvates thereof and pharmaceutically acceptable
178 Chronic Pain
formulations comprising said compounds 1useful for the treatment of depression, anxiety disorders, premature ejaculation, chronic pain, obsessive-compulsive disorder, feeding disorders, premenstrual dysphoric disorder, panic disorders and psychotic disorders including bipolar disorder and schizophrenia. Excerpt(s): This non-provisional application claims priority from provisional application U.S. Ser. No. 60/279,888 filed Mar. 29, 2001, from provisional application U.S. Ser. No. 60/293,122 filed May 23, 2001 and from provisional application U.S. Ser. No. 60/327,804 filed Oct. 9, 2001. The present invention relates to cyclopropylindole derivatives and pharmaceutical compositions comprising said derivatives useful for the treatment of various psychiatric disorders and premature ejaculation. Selective serotonin reuptake inhibitors (SSRIs) are effective for the treatment of mental depression and have been reported to be useful for treating chronic pain. See R. W. Fuller, Pharmacologic Modification of Serotonergic Function: Drugs for the Study and Treatment of Psychiatric and Other Disorders," J. Clin. Psychiatry, 47:4 (Suppl.) April 1986, pp. 4-8 and Selective Serotonin Reuptake Inhibitors. Edited by J P Feighner and W F Boyer, Chichester, England. John Wiley & Sons, 1991, pp 89-108. SSRI's have also demonstrated efficacy for the treatment of anxiety disorders. More recently, SSRI's have demonstrated efficacy in the treatment of premature ejaculation. See Kim and Paick, Short-term Analysis of the Effects of As Needed Use of Sertraline at 5 pm for the Treatment of Premature Ejaculation, Urology 54:544-547 (1999); Kim and Paick, Self Therapy with Sertraline given PRN at 5 pm in treatment of Premature Ejaculation, Journal of Urology 54:544-547 (1998); McMahon and Touma, Treatment of Premature Ejaculation with Paroxetine Hydrochloride As Needed: 2 Single-Blind Placebo Controlled Crossover Studies Journal of Urology 161:1826-1830 (1999); Haensal et al., Clomipramine and sexual function in men with premature ejaculation and controls Journal of Urology 158:1310-1315 (1998); and McMahon and Touma, Treatment of Premature Ejaculation with Paraoxetine Hydrochloride International Journal Impotence Research 11:241-246 (1999). Thus novel SSRI's effective for the treatment of these and other disorders would be greatly advantageous. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Extracts of celery seed for the prevention and treatment of pain, inflammation and gastrointestinal irritation Inventor(s): Butters, Desley Ethel; (Stones Corner, AU), Davis, Craig Kendall Charles; (Chapel Hill, AU), McGeary, Ross Peter; (St Lucia, AU), Powanda, Michael Christopher; (Mill Valley, CA), Rainsford, Kim Drummond; (Baslo, GB), Whitehouse, Michael Wellesley; (Stones Corner, AU) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030206980 Date filed: April 22, 2003 Abstract: Biologically active extracts of celery seed are produced by controlled ethanolic extraction, distillation and drying, and further processing by supercritical fluid extractions (SFE), and may be further fractionated by column fractionation, distillation, LiAlH reduction and the like. These extracts possess activity for the treatment and prevention of acute and chronic pain, inflammation and gastrointestinal irritation.
Patents 179
Excerpt(s): This application is a Continuation of prior U.S. application Ser. No. 09/432,140 filed Nov. 2, 1999, which claims the benefit under 35 U.S.C.sctn.119(a) of prior foreign Australian application nos. PP7975 filed Dec. 30, 1998 and PP6891 filed Nov. 4, 1998, all of which are incorporated herein by reference. This invention relates to the preparation and use of biologically active celery seed extracts that alone and in combination with drugs and herbal medicines can be used to prevent and treat pain, inflammation and gastrointestinal irritation. The prevention or inhibition of inflammation and pain is of significant concern, particularly for those afflicted with arthritis and other musculoskeletal ailments, including sports-related injuries. Pain usually accompanies inflammation and vice versa. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Heterocycle derivatives and drugs Inventor(s): Mori, Kazuya; (Kyoto-Shi, JP), Okano, Masahiko; (Nagaokakyo-Shi, JP) Correspondence: Greenberg Traurig; 21st Floor; 885 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030119855 Date filed: September 25, 2002 Abstract: There is provided an excellent novel analgesic having an analgesic effect which is effective widely against a pain including a chronic pain or an allodynia accompanied with herpes zoster by acting on a nociceptin receptor.The present invention relates to a compound represented by the following formula: 1or a salt thereof.In the formula, X and Y are same or different and each represents a nitrogen atom or CH; R.sup.1 represents a hydrogen atom or alkyl and the like; A.sup.1 and A.sup.2 are same or different and each represents a single bond or a divalent aliphatic hydrocarbon group; Q represents a single bond, cycloalkylene group, phenylene group or divalent heterocyclic group; R.sup.2A, R.sup.2B, R.sup.2C and R.sup.2D are same or different and each represents a hydrogen atom, alkyl or phenyl; E represents a ethenylene group or --NRCO-- (in which R is hydrogen or alkyl) and the like; R.sup.3 represents a phenyl group or a heterocyclic group; R.sup.4 and R.sup.5 are same or different and each represents a hydrogen atom, alkyl, alkoxy, aralkyloxy, halogen, nitro, hydroxy, alkoxycarbonyl, --NR.sup.6R.sup.7 (in which R.sup.6 and R.sup.7 are same or different and each represents a hydrogen atom or alkyl) and the like. Excerpt(s): The present invention relates to a pharmaceutically useful novel heterocyclic derivative or a salt thereof, and a pharmaceutical composition containing the same as an active ingredient. As an analgesic, a narcotic analgesic (such as morphine), a nonnarcotic analgesic (such as aspirin or indomethacin) or a narco-antagonistic analgesic (such as pentazocine) is employed. A narcotic analgesic exerts its analgesic effect mainly by inhibiting a central algesic excitatory transmission. A non-narcotic analgesic exerts its analgesic effect mainly by inhibiting the production of a peripheral dolorogenic substance. A narco-antagonistic analgesic exerts its analgesic effect in a mechanism similar to that of a narcotic analgesic. However, there is no analgesic which is effective against a chronic pain which is not suppressed by morphine, an allodynia accompanied with herpes zoster or hyperalgesia, and an excellent analgesic has been desired to be created. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
180 Chronic Pain
•
Human vanilloid receptor-like proteins Inventor(s): Shinjo, Katsuhiro; (Chita-gun, JP), Yabuuchi, Hikaru; (Yokohama, JP) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030017527 Date filed: May 30, 2001 Abstract: This invention relates to human vanilloid receptor-like protein 2 (VRL-2) polypeptides, polynucleotides encoding such polypeptides, polynucleotide probes or primers, expression vectors and host cells comprising such DNA molecules. This invention further relates to a process for producing the polypeptides; an antibody immunospecific for the polypeptide; a diagnostic kit for diagnosing the VRL-2 receptor related disease; a method for screening to identify modulators which modulate the polypeptides; modulators identified by the screening method; a pharmaceutical composition for treatment of conditions associated with biological function of the polypeptides; and a non-human transgenic animal model for vanilloid receptor-like gene. The polypeptides and the DNA molecules of the present invention can be used to identify agonists, antagonists or the like. These agonists and antagonists are useful for treatment of diseases such as pain, nociceptive pain, chronic pain, neuropathic pain, postoperative pain, cancer pain, rheumatoid arthritic pain, osteoarthritis, diabetic neuropathies, neuralgia, neuropathies, algesia, nerve injury, muscle-skeletal pain, low back pain, neurodegeneration, stroke, inflammatory disorders, athma, allergy, urogenital disorders, incontinence, hypertension, hypotension, perivasular disease and the like. Excerpt(s): The analgesic properties of capsaicin and capsaicinoides are known for their uses in the treatment of a variety of disorders such as pain, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration stroke incontinence and inflammatory disorders (e.g., Campbell et al. "Clinical Applications of Capsaicin and Its Analogues" in Capsaicin in the Study of Pain, Academic Press pgs. 255-272 (1993)). Capsaicin receptors are believed to be members of the ion channel family of polypeptides. These receptors are believed to be associated with the mechanism of action of capsaicin (a vanilloid compound). Capsaicin elicits a senstation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system (e.g, Caterina, M. J. eta al., "The Capsaicin Receptor: A Heat Activated Ion Channel In the Pain Pathway", Nature 389, 816-824 (1997) and Caterina, M. J. et al., "A Capsaicin-Receptor Homologue with A High Threshold For Noxious Heat", Nature 398, 436-441 (1999)). The channels are permeable to cations and exhibit a notable preferance for divalent cations, particularly calcium ions. The level of calcium ion permeability exceeds that observed for most non-selective cation channels and is similar to values observed for NMDA-type glutamate receptors and alpha-7 nicotinic acetylcholine receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 181
•
Mammalian relaxin receptors Inventor(s): Hsu, Sheau Yu; (Mountain View, CA), Hsueh, Aaron J.W.; (Stanford, CA) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030088884 Date filed: August 15, 2002 Abstract: High affinity relaxin receptors, polypeptide compositions related thereto, as well as nucleotide compositions encoding the same, are provided. These proteins, herein termed LGR7 and LGR8, are orphan leucine-repeat-containi- ng, G protein-coupled receptors. These receptors have a wide and a unique tissue expression pattern. The receptors, particularly soluble fragments thereof, are useful as therapeutic agents capable of inhibiting the action of relaxin and InsL3. The receptors and fragments thereof also find use in the screening and design of relaxin agonists and antagonists. Conditions treatable with relaxin agonists or antagonists include prevention or induction of labor, treatment of endometriosis, treatment of skin conditions such as scleroderma that require collagen or extracellular matrix remodelling. Additionally, relaxin has been implicated in the dilation of blood vessels' smooth muscle cells directly and through release of nitric oxide and atrial natriuretic peptide. Relaxin has also been used in the treatment of severe chronic pain, particularly pain arising from stretching, swelling, or dislocation of tissues. Excerpt(s): Relaxin is a pregnancy hormone discovered in 1926 (Hisaw (1926) Proc. Soc. Exp. Biol. Med. 23: 661-663), based on its ability to relax the public ligament in guinea pig. Mature human relaxin is a hormonal peptide of approximately 6000 daltons known to be responsible for remodelling the reproductive tract before parturition, thus facilitating the birth process. A concise review of relaxin was provided by Sherwood, D. in The Physiology of Reproduction, Chapter 16, "Relaxin", Knobil, E. and Neill, J., et al. (eds.), (Raven Press Ltd., New York), pp. 585-673 (1988). Relaxin has local autocrine and/or paracrine roles that contribute to connective tissue remodeling at the maternalfetal interface during late pregnancy and at parturition, including an increase in the expression of the genes, proteins, and enzyme activities of the matrix metalloproteinases interstitial collagenase (MMP-1), stromelysin (MMP-3), and gelatinase B (MMP-9). Two human gene forms of relaxin have been identified, (H1) and (H2) (Hudson et al. (1983) Nature 301:628-631; Hudson et al. (1984) EMBO Journal 3:2333-2339; U.S. Pat. Nos. 4,758,516 and 4,871,670). Only the H2 form is expressed in corpus luteum. The primary translation product of H2 relaxin is a preprorelaxin consisting of a 24 amino acid signal sequence followed by a B chain of about 29 amino acids, a connecting peptide of 104-107 amino acids, and an A chain of about 24 amino acids. Although relaxin itself has been well-characterized for a number of years, it's receptor has remained elusive. To date, binding studies have had to rely on crude cellular extracts, which indicated that a specific binding molecule was present, but gave no clue as to its molecular identity. Relaxin binding sites have been reported in the reproductive tract (Kohsaka et al. (1998) Biol Reprod 59(4):991-9), as well as other tissues, including cardiac and other smooth muscle, and specific nuclei in the brain (Tan et al. (1999) Br J Pharmacol 127(1):91-8). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
182 Chronic Pain
•
Method of administering high-dose, oral magnesium for treatment of chronic pain syndrome or erythromelalgia Inventor(s): Cohen, Jay S.; (Del Mar, CA) Correspondence: Schnader Harrison Segal & Lewis, Llp; 1600 Market Street; Suite 3600; Philadelphia; PA; 19103 Patent Application Number: 20030091655 Date filed: November 12, 2002 Abstract: A method of treating patients, particularly for pain and/or symptoms of erythromelalgia, and other neurovascular or neuropathic disorders, etc. involves administering high doses of magnesium. The magnesium is introduced through several daily administrations, totaling approximately 2-12 times the RDA for magnesium. These higher levels are achieved through increasing daily dosage amounts gradually in response to patient tolerance and until beneficial results are seen. Total magnesium intake is divided over several doses per day and taken with copious amounts of water. Excerpt(s): This application claims the benefit of U.S. provisional patent application Ser. No. 60/334,729, filed Nov. 15, 2001. This invention is in the field of oral pharmaceuticals, and especially in pain management. Magnesium is the seventh most plentiful element in the human body and the most common intracellular divalent cation. A cofactor in hundreds of enzymatic processes, including all enzymes utilizing adenosine triphosphate, magnesium's multiple physiologic effects have been recognized for decades. Clinical studies have suggested that magnesium, as a pharmacologic agent, may be beneficial in many disorders including asthma, cardiac arrhythmias, eclampsia, headaches including migraines, hypertension, mania, mitral valve prolapse, muscle cramps, pain syndromes, various menstrual symptoms, seizures, tetanus, and vasospastic disorders. However, the results from various studies have not been unequivocal. These varied results may be due in part to the limited pharmacologic effects of usual oral dosages of 250-500 mg/day, doses that hardly differ from the recommended daily allowances for magnesium of 350 mg/day for women and 420 mg/day for men. The use of higher oral doses has typically been precluded because of magnesium's tendency to provoke diarrhea in many patients when administered orally. For example, in one study a dosage of 250 mg two times daily of magnesium administered orally produced adverse effects in 45.7% of subjects. Yet oral dosing is without question the administration route of choice. Intravenous drug administration requires that the patient be in a hospital or clinic. Where the condition being treated is chronic, this is impractical. Oral administration at pharmacologic doses is key to treating chronic conditions. However oral dosing at pharmacologic levels has heretofore been ineffective due to the inability of patients to tolerate such a regimen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Method of alleviating chronic pain via peripheral glutaminase regulation Inventor(s): Miller, Kenneth E.; (Sapulpa, OK) Correspondence: Dunlap, Codding & Rogers, P.C.; Attention: Kathryn L. Hester, PH.D.; P. O. Box 16370; Oklahoma City; OK; 73113; US Patent Application Number: 20030072746 Date filed: September 13, 2002
Patents 183
Abstract: A composition having sustained pain-relieving properties such that the composition may be administered to a subject to alleviate chronic pain. The composition includes an effective amount of at least one glutaminase inhibitor. A method for alleviating chronic pain in a subject for an extended period of time is also disclosed, in which the compound is administered to a subject suffering from chronic pain at a site of inflammation such that the administration of the compound results in a reduction in at least one of thermal and mechanical pain responses at the site of inflammation for a period of at least two days without any resulting acute pain behavior. The composition may further include an effective amount of at least one compound having analgesic effects such that the composition also alleviates acute pain. Excerpt(s): The present application claims benefit under 35 U.S.C. 119(e) of U.S. Serial No. 60/318,861, filed Sep. 13, 2001, and Attorney Docket No. 5834.044, U.S. Serial No. not yet assigned, filed Sep. 13, 2002, the contents of which are hereby expressly incorporated herein by reference. The present invention generally relates to methods of alleviating pain, and more particularly, but not by way of limitation, to a method of alleviating chronic pain by regulation of neurotransmitter synthesis. Chronic inflammatory pain is a debilitating condition causing suffering, loss of work and loss of revenue. Several methods of relieving pain from chronic inflammatory conditions such as rheumatoid arthritis, muscle damage, and osteoarthritis are known in the art. However, the prior art methods of relieving pain have several unpleasant or serious side effects and require multiple daily administrations to be effective. For example, narcotics can be used for refractory chronic pain, but administration of narcotics has many side effects, including respiratory depression as well as the possibility of abuse. Additionally, another current method for relief of peripheral pain is topical application of capsaicin cream. This method may be effective for several days but produces severe acute pain in many patients. Further, some pain conditions such as myofascial pain and neuropathies due to nerve injury or disease currently do not have any effective therapies for alleviating pain associated therewith. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and compositions for aiding in smoking cessation and for treating pain and other disorders using optically pure (+)-bupropion Inventor(s): McCullough, John R.; (Hudson, MA), Rubin, Paul D.; (Sudbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20030096873 Date filed: October 23, 2002 Abstract: Methods and compositions are disclosed utilizing the optically pure (+)-isomer of bupropion to assist in smoking cessation, for treating smoking and nicotine addiction, and for treating pain, including, but not limited to, chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders such as narcolepsy, chronic fatigue syndrome, fibromyalgia, seasonal affective disorder and premenstrual syndrome, while avoiding adverse affects associated with racemic bupropion. Excerpt(s): This invention relates to methods and pharmaceutical compositions for aiding smoking cessation, treating nicotine addiction, and pain, including chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the
184 Chronic Pain
plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and 1 are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.energic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and compositions for modulating alpha adrenergic receptor activity Inventor(s): Chow, Ken; (Newport Coast, CA), Fang, Wenkui Ken; (Irvine, CA), Garst, Michael E.; (Newport Beach, CA), Gil, Daniel W.; (Corona Del Mar, CA), Wheeler, Larry A.; (Irvine, CA) Correspondence: Carlos A. Fisher; Allergan, INC.; T2-7h; 2525 Dupont Drive; Irvine; CA; 92612; US Patent Application Number: 20030092766 Date filed: October 19, 2001 Abstract: Methods and compositions for the treatment of pain and intraocular pressure. Particularly disclosed are new compositions for the treatment of chronic pain, glaucoma and methods for their use. Excerpt(s): Human adrenergic receptors are integral membrane proteins which have been classified into two broad classes, the alpha and the beta adrenergic receptors. Both types mediate the action of the peripheral sympathetic nervous system upon binding of catecholamines, norepinephrine and epinephrine. Norepinephrine is produced by adrenergic nerve endings, while epinephrine is produced by the adrenal medulla. The binding affinity of adrenergic receptors for these compounds forms one basis of the classification: alpha receptors tend to bind norepinephrine more strongly than epinephrine and much more strongly than the synthetic compound isoproterenol. The preferred binding affinity of these hormones is reversed for the beta receptors. In many tissues, the functional responses, such as smooth muscle contraction, induced by alpha receptor activation are opposed to responses induced by beta receptor binding. Subsequently, the functional distinction between alpha and beta receptors was further highlighted and refined by the pharmacological characterization of these receptors from various animal and tissue sources. As a result, alpha and beta adrenergic receptors were further subdivided into.alpha.sub.1,.alpha.sub.2,.beta.sub.1, and.beta.sub.2 subtypes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 185
•
Methods and compositions for the treatment and diagnosis of pain disorders using 46566 Inventor(s): Silos-Santiago, Inmaculada; (Del Mar, CA) Correspondence: Tracy M. Sioussat; Millennium Pharmaceuticals, INC.; 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20030091570 Date filed: October 28, 2002 Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of pain disorders, including, but not limited to, inflammatory pain, chronic pain and/or neuropathic pain. The invention further provides methods for identifying a compound capable of treating a pain disorder or modulating pain and/or inflammation response. The invention further provides a method for modulating pain and/or inflammation in a subject. In addition, the invention provides a method for treating a subject having a pain disorder characterized by aberrant 46566 polypeptide activity or aberrant 46566 nucleic acid expression. Excerpt(s): This application claims priority to U.S. provisional application No. 60/335,078, filed Oct. 31, 2001, the contents of which are herein incorporated by reference. Pain is initiated when the peripheral terminals of a subgroup of sensory neurons are activated by noxious chemical, mechanical or thermal stimuli. These neurons, called nociceptors, transmit information regarding tissue damage to painprocessing centers in the spinal cord and brain (Fields, H. L. Pain, McGraw-Hill, New York, 1987). Once a nociceptor is activated, a chain of events occur that transmit this sensation to the brain to be perceived as pain. An important step in this process is the generation of an action potential in a neuron. An action potential results in the accumulation of calcium ions in the axon terminal. This accumulation of calcium causes a release of neurotransmitter into the synapse and the propagation, ultimately, of the information regarding pain to the next neuron in the pathway from the nociceptor to the brain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Methods for the treatment and prevention of neurodegenerative conditions Inventor(s): Abou-Gharbia, Magid A.; (Princeton Junction, NJ), Barrett, James E.; (Washington Crossing, PA), Childers, Wayne E. JR.; (New Hope, PA), Moyer, John A.; (New Hope, PA) Correspondence: Rebecca R. Barrett; 5 Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030092753 Date filed: August 26, 2002 Abstract: Adatanserin is useful for treating neurodegenerative disorders, chronic pain, and other disorders associated with dysfunctional glutamate release. Methods of treating the same comprise administering a therapeutically effective amount of adatanserin or a pharmaceutical salt thereof, to a patient in need of said treatment. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. ______ Not Yet Known, filed Nov. 12, 1999. Glutamate is the predominant neurotransmitter in the central nervous system and it plays an important role in neuroplasticity. As such, excessive extracellular levels of glutamate have been associated
186 Chronic Pain
with the pathophysiology of both acute neurodegenerative disorders such as stroke, transient ischemic attack and spinal/brain trauma, as well as chronic neurodegenerative disorders such as epilepsy, Alzheimer's Disease, amyotrophic lateral sclerosis, Huntington's Disease, Parkinson's Disease, AIDS dementia and retinal diseases (Holt, W. F. et al., Glutamate in Health and Disease: The Role of Inhibitors. In: Neuroprotection in CNS Diseases. Bar, P. R. and Beal, M. F., ed., Marcel Dekker, Inc., New York 1997, pp. 87-199; Engelsen, B. A. et al., Alterations in Excitatory Amino Acid Transmitters in Human Neurological Disease and Neuropathology. In: Neurotoxicity of Excitatory Amino Acids. Guidotti, A., ed., Raven Press Ltd., New York 1990, pp. 311-332; Ince, P. G. et al., The Role of Excitotoxicity in Neurological Disease. Res. Contemp. Pharmacother. 1997, 8, 195-212; Meldrum, B. S. The Glutamate Synapse as a Therapeutical Target: Perspective for the Future. Prog. Brain. Res. 1998, 441-458). Compounds which inhibit the release of glutamate would be expected to be useful in the treatment of chronic diseases in which glutamate dysfunction plays a role, such as chronic neurodegeneration, Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, epilepsy, schizophrenia, AIDS dementia and retinal diseases. Compounds which inhibit or attenuate the release of glutamate would also represent potential neuroprotective agents for the treatment of ischemia resulting from stroke, transient ischemic attack and brain/spinal trauma (Koroshetz, W. J. and Moskowitz, M. A., Emerging Treatment for Stroke in Humans. Trends in Pharmacol. Sci 1996, 17, 227-233; Dunn, C. D. R. Stroke: Trends, Treatments and Markets. Scrip Reports, PJB Publications, Richmond 1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for the treatment of chronic pain and compositions therefor Inventor(s): Buxton, Francis Paul; (Morristown, NJ), Ganju, Pamposh; (London, GB), Snell, Christopher Robert; (Runcton Holme, GB), Song, Chuanzheng; (Warren, NJ) Correspondence: Thomas Hoxie; Novartis, Patent And Trademark Department; One Health Plaza 430/2; East Hanover; NJ; 07936-1080; US Patent Application Number: 20030144234 Date filed: August 28, 2002 Abstract: The invention discloses cathepsin S as a suitable target for the development of new therapeutics to treat or ameliorate chronic pain. The invention relates to methods to treat and/or ameliorate chronic pain and pharmaceutical compositions therefor comprising modulators with inhibitory effect on cathepsin S enzyme activity and/or cathepsin S gene expression. The invention also relates to a method to identify compounds with therapeutic usefulness to treat chronic pain, comprising identifying compounds that can inhibit cathepsin S activity and/or gene expression which can also reverse the pathological effects of chronic pain in vivo. Excerpt(s): Pain is a term that encompasses a spectrum of clinical states. Under normal conditions acute pain is beneficial and serves as a physiological warning for a potentially tissue-damaging situation. More persistent pain, usually associated with inflammation, can also be regarded as a normal protective response to mild tissue injury and resolves when the injury has healed. However, chronic pain occurs when the stimulus and pain are unrelated and the pain is no longer a protective mechanism. These types of pain syndromes (e.g. rheumatoid arthritis, cancer pain, neuropathic pain) are notoriously difficult to treat. It is estimated that 10-20% of the adult population suffers from chronic pain. To date, the main analgesics employed are based on opiates
Patents 187
and non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin. Both classes of drugs can produce severe side-effects; NSAIDS can cause gastric ulceration and renal damage while opiates can cause nausea, constipation, confusion and dependency problems. Despite these disadvantages, no new class of analgesics have been discovered or developed recently; there is clearly a need for additional therapies for chronic pain. Chronic pain states are characterised by a number of clinical features. As well as spontaneous pain, patients may exhibit hyperalgesia (a greatly exaggerated response to a noxious mechanical, hot, or cold stimulus), and allodynia (previously non-noxious stimuli are now perceived as painful). All these features result from a complex series of events involving changes in the function of sensory nerves in the periphery and in the processing of sensory information in the spinal cord and brain. These changes occur in response to direct neuronal damage or in response to mediators released during tissue damage or inflammation. Broadly speaking, chronic pain syndromes can be defined as inflammatory (also known as nociceptive) or neuropathic. Chronic inflammatory pain, as its name suggests, occurs during conditions in which there is underlying inflammation such as rheumatoid arthritis, burns, muscle damage or surgical wounds. Knowledge of the mechanisms underlying inflammatory pain has advanced considerably over recent years and it is known to involve a variety of mediators and their activation and sensitization of the peripheral terminals of sensory nerves and the consequent longer term changes in reactivity of spinal cord neurons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel human nucleic acid molecules and polypeptides encoding a novel human ion channel expressed in spinal cord and brain Inventor(s): Feder, John N.; (Belle Mead, NJ), Gaughan, Glen T.; (Northford, CT), Mintier, Gabe; (Hightstown, NJ), Nelson, Thomas C.; (Lawrenceville, NJ), Ramanathan, Chandra S.; (Wallingford, CT) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030027164 Date filed: November 30, 2001 Abstract: The present invention relates to novel human nucleic acid molecules encoding novel human cation channels, and proteins and polypeptides encoded by such nucleic acid molecules. More specifically, the nucleic acid molecules of the invention include novel human genes, e.g., hVR1d.1 and hVR1d.2, that encode proteins or polypeptides that are expressed in spinal cord and brain tissues and display sequence homology and structural homology to the vanilloid and TRP (transient receptor potential) families of cation channel proteins. The proteins and polypeptides of the invention directed to this novel human cation channel may be therapeutically valuable targets for drug delivery in the treatment of human diseases that involve calcium, sodium, potassium or other ionic homeostatic dysfunction, such as central nervous system (CNS) disorders, e.g., degenerative neurological disorders such as Alzheimer's disease or Parkinson's disease, or other disorders such as chronic pain, anxiety and depression, stroke, cardiac disorders, e.g., arrhythmia, diabetes, hypercalcemia, hypocalcemia, hypercalciuria, hypocalciuria, or ion disorders associated with immunological disorders, gastrointestinal (GI) tract disorders or renal or liver disease. Excerpt(s): This application claims benefit to provisional application U.S. Serial No. 60/250,587, filed Dec. 1, 2000. The present invention relates to the isolation and
188 Chronic Pain
identification of novel human nucleic acid molecules and proteins and polypeptides encoded by such nucleic acid molecules, or degenerate variants thereof, encoding novel human ion channels. More specifically, the nucleic acid molecules of the invention relate to a novel human gene, termed hVR1d, that encodes proteins or polypeptides that are expressed in spinal cord and brain tissues and display sequence homology and structural homology to the 20 vanilloid and TRP (transient receptor potential) families of cation channel proteins. The proteins and polypeptides of the invention directed to this novel human cation channel may be therapeutically valuable targets for drug delivery in the treatment of human diseases that involve calcium, sodium, potassium or other ionic homeostatic dysfunction, such as central nervous system (CNS) disorders, e.g., degenerative neurological disorders such as Alzheimer's disease or Parkinson's disease, or other disorders such as chronic pain, anxiety and depression, stroke, cardiac disorders, e.g., arrhythmia, diabetes, hypercalcemia, hypocalcemia, hypercalciuria, hypocalciuria, or ion disorders associated with immunological disorders, gastrointestinal (GI) tract disorders or renal or liver disease. Control of the internal ionic environment is an extremely important function of all living cells. Ion exchange with the external medium is regulated by a variety of means, the most important of which are various transporters and ion channels. Ion channels comprise a very large and diverse family of proteins which play an important role in cell homeostasis, hormone and neurotransmitter release, motility, neuronal action potential generation and propagation and other vital intra- and inter-cellular functions. Thus, these channels are important targets for the development of therapeutic compounds in the treatment of disease. A number of proteins have been described as forming ion channels, including the vanilloid and TRP protein families. These proteins have been shown to function as cation channels of varying degrees of selectivity and with different, and in some cases unknown, mechanisms for channel gating. For example, the TRP family of ion channels comprises a group of proteins some of which are believed to form store-operated calcium (Ca.sup.2+) channels, i.e., ion channels that operate to allow the influx of extracellular Ca.sup.2+ into cells when the intracellular stores of calcium are depleted (Zhu et al., 1996, Cell 85: 661-671). It is believed that TRP ion channels are expressed, in some form, in most, if not all, animal tissues (Zhu et al., supra at 661). In addition, another protein, termed trp-like or trpl, has been disclosed (Phillips et al., 1992, Neuron 8: 631-642; Gillo et al., 1996, PNAS USA 93: 14146-14151) and it has been suggested that there may be a cooperative interaction between TRP and TRPL proteins, perhaps these proteins contributing channel subunits to form a multimeric Ca.sup.2+ channel (Gillo et al., supra). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel thiourea compounds and the pharmaceutical compositions containing the same Inventor(s): Kim, Hee Doo; (Seoul, KR), Lee, Jee Woo; (Seoul, KR), Oh, Uh Taek; (Kyunggi-do, KR), Park, Hyeung Geun; (Seoul, KR), Park, Young Ho; (Seoul, KR), Suh, Young Ger; (Kyunggi-do, KR), Yi, Jung Bum; (Kyunggi-do, KR) Correspondence: Finnegan Henderson Farabow; Garrett & Dunner; 1300 I Street NW; Washington; DC; 20005; US Patent Application Number: 20030212140 Date filed: February 20, 2003 Abstract: The present invention relates to thiourea compounds and the pharmaceutical compositions containing the same, and particularly, to novel thiourea compounds as an
Patents 189
antagonist against vanilloid receptor (VR) and the pharmaceutical compositions thereof. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides a pharmaceutical composition for prevention or treatment of these diseases. Excerpt(s): The present invention relates to thiourea compounds and the pharmaceutical compositions containing the same, and particularly, to thiourea compounds with superior efficacy as an antagonist against vanilloid receptor (VR) and the pharmaceutical compositions thereof. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomachduodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides pharmaceutical compositions for prevention or treatment of these diseases. Yet, the diseases described above are only for enumeration, not to limit the scope of clinical application of vanilloid receptor antagonist. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel use of peptide class of compound for treating non neuropathic inflammatory pain Inventor(s): Selve, Norma; (Troisdorf, DE) Correspondence: Edwards & Angell, Llp; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20030171300 Date filed: February 11, 2003 Abstract: The present invention concerns the use of compounds of the Formula (I) for treating different types and symptoms of acute and chronic pain, especially non neuropathic inflammatory pain in mammals. The pain to be treated may be e.g. chronic inflammatory pain, rheumatoid arthritis pain and/or secondary inflammatory osteoarthritic pain. The compounds show an antinociceptive profile and differ from classical analgesics like opioids and non-steroidal anti-inflammatory drugs (NSAIDS) and are useful as specific analgesics. Excerpt(s): The present invention is directed to the novel use of a peptide class of compound for treating different types and symptoms of acute and chronic pain, especially non neurophathic inflammatory pain. a is 1-3. Ar is aryl which is unsubstituted or substituted with halo; R.sub.3 is lower alkoxy; and R.sub.1 is lower alkyl especially methyl. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
190 Chronic Pain
•
Pharmaceutical composition for treatment of acute, chronic pain and/or neuropathic pain and migraines Inventor(s): Coe, Jotham W.; (Niantic, CT), Harrigan, Edmund P.; (Old Lyme, CT), O'Neill, Brian T.; (Old Saybrook, CT), Sands, Steven B.; (Stonington, CT), Watsky, Eric J.; (Stonington, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20030133951 Date filed: January 21, 2003 Abstract: Pharmaceutical compositions are disclosed for the treatment of acute, chronic and/or neuropathic pain. The pharmaceutical compositions are comprised of a therapeutically effective combination of a nicotine receptor partial agonist and an analgesic agent and a pharmaceutically acceptable carrier. The analgesic agent is selected from opioid analgesics, NMDA antagonists, substance P antagonists, COX 1 and COX 2 inhibitors, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), capsaicin receptor agonists, anesthetic agents, benzodiazepines, skeletal muscle relaxants, migraine therapeutic agents, anti-convulsants, antihypertensives, anti-arrythmics, antihistamines, steroids, caffeine, and botulinum toxin. The method of using these compounds and a method of treating acute, chronic and/or neuropathic pain and migraine in a mammal including a human is also disclosed. Excerpt(s): The present invention relates to pharmaceutical compositions for the treatment of acute, chronic and/or neuropathic pain and migraine in a mammal (e.g. human) comprising a nicotine receptor partial agonist (NRPA) and analgesic agents, including opioid analgesics, NMDA antagonists, substance P antagonists, COX 1 and COX 2 inhibitors, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), capsaicin receptor agonists, anesthetic agents, benzodiazepines, skeletal muscle relaxants, migraine therapeutic agents, anti-convulsants, anti-hypertensives, antiarrythmics, antihistamines, steroids, caffeine, N-type calcium channel antagonists and botulinum toxin. The term NRPA refers to all chemical compounds which bind at neuronal nicotinic acetylcholine specific receptor sites in mammalian tissue and elicit a partial agonist response. A partial agonist response is defined here to mean a partial, or incomplete functional effect in a given functional assay. Additionally, a partial agonist will also exhibit some degree of antagonist activity by its ability to block the action of a full agonist (Feldman, R. S., Meyer, J. S. & Quenzer, L. F. Principles of Neuropsychopharmacology, 1997; Sinauer Assoc. Inc.). The present invention may be used to treat mammals (e.g. humans) for acute, chronic and/or neuropathic pain with a decrease in the severity of unwanted side effects such as causing nausea and/or stomach upset. The invention also relates to aryl fused azapolycylic compounds that bind to neuronal nicotinic acetylcholine specific receptor sites and are useful in modulating cholinergic function and are referred to in WO 9818798-A1, WO 9935131-A1 and WO 9955680-A1. The foregoing applications are owned in common with the present application and are incorporated herein by reference in their entireties. Analgesic agents decrease pain perception. In animal models of pain states, the above compounds inhibit acute pain perception. These compounds also inhibit pain sensitization processes in which the perception of the painfulness of a given stimulus is increased without any change in stimulus intensity. In humans, analgesic agents have also been found to decrease both acute pain perception and sensitization. Opioid analgesic agents, in particular, remain the most effective means of alleviating severe pain across a broad spectrum, including inflammatory as well as neuropathic pain states. However, even
Patents 191
though analgesic agents have therapeutic utility in the treatment of pain, there are significant liabilities to the use of analgesic compounds. Specifically, many of these compounds that have been tested in humans can cause potentially serious side effects such as gastrointestinal complications including nausea, emesis, ulcers, and constipation, respiratory depression, and psychological and physical dependence. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Piperidine derivatives as subtype selective N-methyl-D-aspartate antagonists Inventor(s): Kornberg, Brian Edward; (Ann Arbor, MI), Lewthwaite, Russell Andrew; (Cambridge, GB), Manning, David; (Duanesburg, NY), Nikam, Sham Shridhar; (Ann Arbor, MI), Scott, Ian Leslie; (Delanson, NY) Correspondence: David R. Kurlandsky; Warner-lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030018021 Date filed: November 30, 2001 Abstract: Described are piperidines of Formula I 1and pharmaceutically acceptable salts thereof. The compounds of Formula I are antagonists of NMDA receptor channel complexes useful for treating cerebral vascular disorders such as, for example, stroke, cerebral ischemia, central nervous system disorders, depression, trauma, hypoglycemia, neurodegenerative disorders, anxiety, migraine headache, convulsions, Parkinson's disease, aminoglycoside antibiotics-induced hearing loss, psychosis, glaucoma, CMV retinitis, opioid tolerance or withdrawal, pain, especially chronic pain, neuropathic pain, or surgical pain, or urinary incontinence. Excerpt(s): The invention relates to piperidine derivatives as N-Methyl-D-Aspartate (NMDA) antagonists useful in the treatment of diseases and disorders responsive to antagonism of NMDA receptors. Many of the physiological and pathophysiological effects of the endogenous excitatory neurotransmitter glutamate are mediated via actions at N-Methyl-D-Asparate (NMDA) receptors. Over-excitation of the NMDA receptors on postsynaptic cells-mediated by excessive release of glutamate from nerve endings or glial cells-results in a massive calcium ion influx through a calcium ion channel into neuronal cells, leading to neuronal cell death. These events occur under ischemic or hypoxic conditions such as, for example, stroke, hypoglycemia, cardiac arrest, or acute physical trauma. NMDA receptors in vivo form an NMDA receptor channel complex in cell walls comprising at least three binding domains, including a glutamic acid (or NMDA) recognition site, a channel blocking binding site, and a strychnine-insensitive glycine binding site. Physiologically, a blockade of at least one of these sites terminates the channel opening of the NMDA receptor, thereby preventing calcium ion influx into cells. Accordingly, an NMDA receptor antagonist is therapeutically useful because it minimizes damage to the central nervous system induced by calcium ion influx under ischemic or hypoxic conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
192 Chronic Pain
•
Piperidines Inventor(s): Atkinson, Robert N.; (Raleigh, NC), Gross, Michael F.; (Durham, NC), Johnson, Matthew S.; (Durham, NC) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030171360 Date filed: November 1, 2002 Abstract: Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltagedependent sodium channels. More particularly, the invention provides substituted piperidines, and compositions containing these compounds. Also provided are methods using the compounds of the invention for the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrance of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a channel that includes a PN3 subunit. Excerpt(s): This is a non-provisional filing of U.S. Provisional Patent Application No. 60/335,930, filed on Nov. 1, 2001, the disclosure of which is incorporated herein by reference in its entirety for all purposes. This invention relates to the use of certain piperidine compounds as sodium channel inhibitors and to the treatment of neuropathic pain by the inhibition of sodium channels. Additionally, this invention relates to novel piperidine-based compounds that are useful as sodium channel inhibitors. Sodium channel-blocking agents have been reported to be effective in the treatment of various disease states, and have found particular use as local anesthetics and in the treatment of cardiac arrhythmias. It has also been reported that sodium channel-blocking agents may also be useful in the treatment of pain, including neuropathic pain; see, for example, Tanelian et al. Pain Forum. 4(2), 75-80 (1995). Preclinical evidence demonstrates that sodium channel-blocking agents selectively suppress abnormal ectopic neural firing in injured peripheral and central neurons, and it is via this mechanism that they are believed to be useful for relieving pain. Consistent with this hypothesis, it has been shown that sodium channels accumulate in the peripheral nerve at sites of axonal injury (Devor et al. J. Neurosci. 132: 1976 (1993)). Alterations in either the level of expression or distribution of sodium channels within an injured nerve, therefore, have a major influence on the pathophysiology of pain associated with this type of trauma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Receptor agonists useful for the treatment of pain Inventor(s): Borowsky, Beth E.; (Flemington, NJ), Quan, Yong; (E. Windsor, NJ), Smith, Kelli E.; (Fair Lawn, NJ) Correspondence: Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030022839 Date filed: July 2, 2002
Patents 193
Abstract: This invention provides a method of treating a subject suffering from an abnormality which comprises administering to the subject an amount of a SNORF11 receptor agonist effective to treat the subject's abnormality. This invention further provides a method of treating pain, particularly chronic pain, chronic inflammatory pain and arthritic pain, which comprises administering to the subject an amount of a SNORF11 receptor agonist effective to treat the subject's pain. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/897,201, filed Jul. 2, 2001, which is a continuation-in-part of U.S. Ser. No. 09/266,127, filed Mar. 10, 1999, the contents of which are herein incorporated by reference. Throughout this application various publications are referred to by partial citations within parenthesis. Full citations for these publications may be found at the end of the specification immediately preceding the claims. The disclosures of these publications, in their entireties, are hereby incorporated by reference into this application in order to more fully describe the state of the art to which the invention pertains. Neuroregulators comprise a diverse group of natural products that subserve or modulate communication in the nervous system. They include, but are not limited to, neuropeptides, amino acids, biogenic amines, lipids and lipid metabolites, and other metabolic byproducts. Many of these neuroregulator substances interact with specific cell surface receptors which transduce signals from the outside to the inside of the cell. G-protein coupled receptors (GPCRs) represent a major class of cell surface receptors with which many neurotransmitters interact to mediate their effects. GPCRs are characterized by seven membrane-spanning domains and are coupled to their effectors via G-proteins linking receptor activation with intracellular biochemical sequelae such as stimulation of adenylyl cyclase. While the structural motifs that characterize a GPCR can be recognized in the predicted amino acid sequence of a novel receptor, the endogenous ligand that activates the GPCR cannot necessarily be predicted from its primary structure. Thus, a novel receptor sequence may be designated as an orphan GPCR when it possesses the structural motif characteristic of a G-protein coupled receptor, but its endogenous ligand has not yet been defined. This application describes the identification of several peptide agonists for the GPCR designated SNORF11 receptor, and further describes a novel therapeutic use for such agonists, namely the treatment of pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Regulation of human serotonin-like g protein-coupled receptor Inventor(s): Ramakrishnan, Shyam; (Brighton, MA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030114643 Date filed: September 18, 2002 Abstract: Reagents which regulate human serotonin-like G protein-coupled receptor (5HT-GPCR) and reagents which bind to human 5-HT-GPCR gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to disorders of both the central and the peripheral nervous system, for example in primary and secondary disorders after brain injury, disorders of mood, anxiety disorders, disorders of thought and volition, disorders of sleep and wakefulness, diseases of the motor unit like neurogenic and myopathic disorders, neurodegenerative disorders like Alzheimer's and Parkinson's disease, disorders leading to peripheral and chronic pain.
194 Chronic Pain
Excerpt(s): The invention relates to the area of G-protein coupled receptors. More particularly, it relates to the area of human serotonin-like G protein-coupled receptor and its regulation. Many medically significant biological processes are mediated by signal transduction pathways that involve G-proteins (Lefkowitz, Nature 351, 353-354, 1991). The family of G-protein coupled receptors (GPCR) includes receptors for hormones, neurotransmitters, growth factors, and viruses. Specific examples of GPCRs include receptors for such diverse agents as dopamine, calcitonin, adrenergic hormones, endothelin, cAMP, adenosine, acetylcholine, serotonin, histamine, thrombin, kinin, follicle stimulating hormone, opsins, endothelial differentiation gene-1, rhodopsins, odorants, cytomegalovirus, G-proteins themselves, effector proteins such as phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins such as protein kinase A and protein kinase C. GPCRs possess seven conserved membranespanning domains connecting at least eight divergent hydrophilic loops. GPCRs (also known as 7TM receptors) have been characterized as including these seven conserved hydrophobic stretches of about 20 to 30 amino acids, connecting at least eight divergent hydrophilic loops. Most GPCRs have single conserved cysteine residues in each of the first two extracellular loops, which form disulfide bonds that are believed to stabilize functional protein structure. The seven transmembrane regions are designated as TM1, TM2, TM3, TM4, TM5, TM6, and TM7. TM3 has been implicated in signal transduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted oxindole derivatives as tyrosine kinase inhibitors Inventor(s): Dickerson, Scott Howard; (Durham, NC), Hunter, Robert N; (Durham, NC), Kuyper, Lee Frederick; (Durham, NC), Lackey, Karen Elizabeth; (Durham, NC), Luzzio, Michael J.; (Noank, CT) Correspondence: David J Levy, Corporate Intellectual Property; Glaxosmithkline; Five Moore DR., PO Box 13398; Research Triangle Park; NC; 27709-3398; US Patent Application Number: 20030195234 Date filed: February 27, 2003 Abstract: The present invention is related to oxindole derivatives of structure (I), compositions containing the same, and methods of use and manufacture of the same. Such compounds generally are useful pharmacologically as agents in those disease states alleviated by the alteration of mitogen activated signaling pathways in general, and in particular in the inhibition or antagonism of protein kinases, which pathologically involve aberrant cellular proliferation. Such disease states include tumor growth, restenosis, atherosclerosis, pain and thrombosis, In particular, the present invention relates to a series of substituted oxindole compounds, which exhihit Trk family protein tyrosine kinase inhibition, and which are useful in cancer therapy and chronic pain indications. Excerpt(s): The present invention is related to oxindole derivatives, compositions containing the same, and methods of use and manufacture of the same. Such compounds generally are useful pharmacologically as agents in those disease states alleviated by the alteration of mitogen activated signaling pathways in general, and in particular in the inhibition or antagonism of protein kinases, which pathologically involve aberrant cellular proliferation. Such disease states include tumor growth, restenosis, atherosclerosis, pain and thrombosis. In particular, the present invention relates to a series of substituted oxindole compounds, which exhibit Trk family protein tyrosine kinase inhibition, and which are useful in cancer therapy and chronic pain
Patents 195
indications. Cell growth, differentiation, metabolism and function are very tightly controlled in higher eukaryotes. The ability of a cell to rapidly and appropriately respond to the array of external and internal signals it continually receives is of critical importance in maintaining a balance between these processes (Rozengurt, Current Opinion in Cell Biology 1992, 4, 161-5; Wilks, Progress in Growth Factor Research 1990, 2, 97-111). The loss of control over cellular regulation can often lead to aberrant cell function or death, often resulting in a disease state in the parent organism. The protein kinases represent a large family of proteins which play a central role in the regulation of a wide variety of cellular processes and maintaining control over cellular function (Hanks, et al., Science 1988, 241, 42-52). A partial list of such kinases includes ab1, ATK, bcr-ab1, Blk, Brk, Btk, c-kit, c-met, c-src, CDK1, CDK2, CDK4, CDK6, cRaf1, CSF1R, CSK, EGFR, ErbB2, ErbB3, ErbB4, ERK, Fak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, FLK-4, flt-1, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak, KDR, Lck, Lyn, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie.sub.1, tie.sub.2, TRK,Yes, and Zap70. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted quinazolines and analogs and the use thereof Inventor(s): Cai, Sui X.; (San Diego, CA), Lan, Nancy C.; (Altadena, CA), Upasani, Ravi; (Sunnyvale, CA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W., Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20030033089 Date filed: August 16, 2002 Abstract: The invention relates to novel quinazolines and heterocycles which are antagonists or positive modulators of AMPA receptors, and the use thereof for treating, preventing or ameliorating neuronal loss associated with stroke, global and focal ischemia, CNS trauma, hypoglycemia and surgery, as well as treating or ameliorating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Down's syndrome, treating, preventing or ameliorating the adverse consequences of the overstimulation of the excitatory amino acids, treating, preventing or ameliorating anxiety, psychosis, convulsions, chronic pain, glaucoma, retinitis, urinary incontinence, muscular spasm and inducing anesthesia, as well as for treating or ameliorating the adverse consequences of excitatory amino acid deficiency such as schizophrenia, myoclonus, Alzheimer's disease and malnutrition and neural maldevelopment, and as cognition and learning enhancers. Excerpt(s): This invention is in the field of medicinal chemistry. In particular, the invention is related to novel substituted quinazolines and analogs thereof. These compounds are antagonists of x-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) ionotropic receptors. Certain of these compounds are positive modulators of AMPA receptors. The invention also is directed to the use of novel substituted quinazolines and analogs thereof for the treatment of neuronal damage following global and focal ischemia, and for the treatment or prevention of neurodegenerative conditions, as anticonvulsants, as cognitive enhancers, and for the treatment of schizophrenia, Parkinson's disease and myoclonus. The compounds of the invention are also useful for treatment or prevention of pain, including acute and chronic pain. The invention also is directed to a process for the preparation of the substituted quinazolines and analogs thereof. Excitatory amino acid receptors are classified into two general types. Receptors that are directly coupled to the opening of cation channels in the cell
196 Chronic Pain
membrane of the neurons are termed "ionotropic." This type of receptor has been subdivided into at least three subtypes, which are defined by the depolarizing actions of the selective agonist N-methyl-D-aspartate (NMDA),.alpha.-amino-3-hydroxy-5methylisoxazole-4-- propionic acid (AMPA), and kainic acid (KA). The second general type is the G-protein or second messenger-linked "metabotropic" excitatory amino acid receptor. This second type, when activated by the agonists quisqualate, ibotenate, or trans-1-aminocyclopentane-1,3-dicarboxylic acid, leads to enhanced phosphoinositide hydrolysis in the postsynaptic cell. Both types of receptors appear not only to mediate normal synaptic connections during development, but also change in the efficiency of synaptic transmission throughout life. (Schoepp, Bockaert, and Sladeczek, Trends Pharm. Sci. 11:508 (1990); McDonald and Johnson, Brain Res. Rev. 15:41 (1990)). The excessive or inappropriate stimulation of excitatory amino acid receptors leads to neuronal cell damage or loss by a mechanism known as excitotoxicity. The medical consequences of such neuronal degeneration makes the abatement of these degenerative neurological processes an important therapeutic goal. (See U.S. Pat. No. 5,284,957). Antagonists of the AMPA receptor are considered useful in treating, preventing and ameliorating a number of neurologic disorders which are due to overstimulation by the excitatory amino acids. These include acute neurologic disorders such as domoic acid poisoning; cerebral ischemia, global ischemia associated with cardiac arrest; stroke; spinal cord trauma; hypoxia; anoxia; poisoning by carbon monoxide, manganese or cyanide; hypoglycemia; mechanical trauma to the nervous system; epileptic seizures; and chronic neurologic disorders such as Huntington's disease, neuronal injury associated with HIV and AIDS, AIDS dementia, neuropathic pain syndrome, olivopontocerebral atrophy, Parkinson's disease, amyotrophic lateral sclerosis, mitochondrial abnormalities, Alzheimer's disease, hepatic encephalopathy, Tourette's syndrome, drug addiction and urinary incontinence (see Lipton and Rosenberg, N. Engl. J. Med. 330: 613-622 (1994)) and treatment or amelioration of a number of chronic neurologic disorders such as schizophrenia. AMPA receptor antagonists are also useful in treating, preventing and ameliorating acute and chronic pain, pain associated with post-therapeutic neurolgia, insterstital cystitis, osteoarthritis, spinal cord injury, cancer and diabetic neuropathy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Subtype-selective NMDA receptor ligands and the use thereof Inventor(s): Araldi, Gian Luca; (Washington, DC), Bigge, Christopher F.; (Ann Arbor, MI), Cai, Sui Xiong; (Foothill, CA), Guzikowski, Anthony P.; (Eugene, OR), Keana, John F.W.; (Eugene, OR), Lamunyon, Donald; (Junction City, OR), Lan, Nancy C.; (South Pasadena, CA), Zhou, Zhang-Lin; (Irvine, CA) Correspondence: Fitzpatrick Cella Harper & Scinto; 30 Rockefeller Plaza; New York; NY; 10112; US Patent Application Number: 20030144319 Date filed: November 14, 2002 Abstract: The invention relates to subtype-selective NMDA receptor ligands and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions,
Patents 197
aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, Parkinson's disease, glaucoma, CMV retinitis, urinary incontinence, opioid tolerance or withdrawal, and inducing anesthesia, as well as for enhancing cognition. Excerpt(s): This invention is related to 2-substituted piperidine analogs. The analogs are selectively active as antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 2-substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neurodegenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Excitatory amino acid receptor antagonists that block NMDA receptors are recognized for usefulness in the treatment of disorders. NMDA receptors are intimately involved in the phenomenon of excitotoxicity, which may be a critical determinant of outcome of several neurological disorders. Disorders known to be responsive to blockade of the NMDA receptor include acute cerebral ischemia (stroke or cerebral trauma, for example), muscular spasm, convulsive disorders, neuropathic pain and anxiety, and may be a significant causal factor in chronic neurodegenerative disorders such as Parkinson's disease [T. Klockgether, L. Turski, Ann. Neurol. 34, 585593 (1993)], human immunodeficiency virus (HIV) related neuronal injury, amyotrophic lateral sclerosis (ALS), Alzheimer's disease [P. T. Francis, N. R. Sims, A. W. Procter, D. M. Bowen, J. Neurochem. 60 (5), 1589-1604 (1993)] and Huntington's disease. [See S. Lipton, TINS 16 (12), 527-532 (1993); S. A. Lipton, P. A. Rosenberg, New Eng. J. Med. 330 (9), 613-622 (1994); and C. F. Bigge, Biochem. Pharmacol. 45, 1547-1561 (1993) and references cited therein.]. NMDA receptor antagonists may also be used to prevent tolerance to opiate analgesia or to help control withdrawal symptoms from addictive drugs (Eur. Pat. Appl. 488,959A). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of chronic pain with 3-heterocycloxy-and 3-cycloalkyloxy-3-phenylpropanamines Inventor(s): Robertson, David W.; (Ann Arbor, MI) Correspondence: Pharmacia & Upjohn; 301 Henrietta ST; 0228-32-law; Kalamazoo; MI; 49007; US Patent Application Number: 20030087938 Date filed: July 29, 2002 Abstract: This application relates to the use of certain 3-heterocyclo and 3-cycloalkyloxy3-phenylpropanamines in the treatment of chronic pain, including neuropathic pain.
198 Chronic Pain
Excerpt(s): This application claims the benefit of the following provisional application(s): U.S. Serial No. 60/309,084, filed Jul. 31, 2001, under 35 USC 119(e)(i). Chronic painful conditions, in various forms, affect a considerable number of people including, according to the WHO, 4 million cancer sufferers who, worldwide, suffer as a result of a lack of suitable care. There are a number of other conditions, such as musculoskeletal or vertebral pain, neurological pain, headaches or vascular pain. Neurophathic pain, a chronic pain condition occurring in the setting of nervous system injury or tissue injury, is characterized by unusual sensory experiences (allodynia, hyperalgesia) and abnormal pain processing in the central and peripheral nervous systems; treatment of neuropathic pain is difficult. Painful diabetic neuropathy is one of the most frequent complication of diabetes in humans, post-herpetic neuralgia develops in 10-30% of patients after herpes zoster, phantom limb and stump pain is a common sequela of amputation. Chronic pain may also be caused by a trauma, an entrapment neuropathy (e.g. carpal tunnel syndrome), multiple sclerosis or a polyneurophathy associated with AIDS, alcoholism, hypothyroidism, or anticancer chemotherapy. Conventional treatments of pain fall into two categories: 1) nonsteroidal antiinflammatory drugs (NSAIDS), used to treat mild pain, but whose therapeutic use is limited by GI adverse effects; and 2) morphine and related opiods, used to treat moderate to severe pain but whose therapeutic use is limited by undesirable side effects including respiratory depression, tolerance, and abuse potential. However, conventional analgesics, whether opiates or NSAIDS's, have limited therapeutic value in the management of chronic pain syndromes. This has led to the use of adjuvant analgesics for the management of these conditions. For example, tricyclic antidepressant are currently the first choice in the treatment of painful diabetic neuropathy. However, few agents are fully effective in all patients and undesirable side effects are common. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Vanilloid receptor-2 Inventor(s): Ruben, Steven M.; (Olney, MD), Young, Paul E.; (Gaithersburg, MD) Correspondence: Sterne, Kessler, Goldstein & Fox P.L.L.C.; 1100 New York Avenue, N.W.; Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20030022289 Date filed: May 3, 2002 Abstract: The present invention relates to vanilloid receptor-2, a novel member of the vanilloid receptor family. The invention provides isolated nucleic acid molecules encoding human VR2 receptors. VR2 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of VR2 receptor activity. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of VR2 receptors. Further provided are therapeutic methods for treating disease states including, but not limited to, chronic pain syndromes, congenital pain insensitivity, inflammation, ischemia, host defense dysfunction, immune surveillance dysfunction, arthritis, multiple sclerosis, autoimmunity, immune dysfunction, and allergy. Excerpt(s): The present invention relates to a novel member of the vanilloid receptor family. More specifically, the present invention relates to the discovery, identification and characterization of nucleotides that encode vanilloid receptor-2 (VR2), a receptor having homology with the rat vanilloid receptor-1 protein. The invention encompasses
Patents 199
VR2 polynucleotides, host cell expression systems, VR2 polypeptides (including fragments, variants, derivatives and analogs thereof), VR2 fusion proteins, antibodies to VR2, agonists and antagonists of VR2, and other compounds that modulate VR2 gene expression or VR2 activity, that can be used for diagnosis, drug screening, and treatment or prevention of disorders which include, but are not limited to, chronic pain syndromes, congenital pain insensitivity, inflammation, ischemia, host defense dysfunction, immune surveillance dysfunction, arthritis, multiple sclerosis, autoimmunity, immune dysfunction, and allergy. The concentration of free Ca.sup.+2 in the cytosol of any cell is extremely low (.apprxeq.10.sup.-7 M), whereas the concentration of free Ca.sup.+2 in the extracellular fluid (.apprxeq.10.sup.-3 M) and in the endoplasmic reticulum is quite high. Thus, there is a large gradient tending to drive Ca.sup.+2 into the cytosol across both the plasma membrane and the endoplasmic reticulum membrane. When a signal transiently opens Ca.sup.+2 channels in either of these membranes, Ca.sup.+2 rushes into the cytosol, dramatically increasing the local Ca.sup.+2 concentration and triggering Ca+.sup.2-responsive proteins in the cell. Ca.sup.+2 has been demonstrated to act as an intracellular messenger in a wide variety of cellular responses, such as, for example, transmission of an action potential in nerve cells, muscular contraction, and cell secretion, activation, survival, proliferation, migration, and differentiation. Pain is initiated when a subgroup of sensory neurons, called nociceptors, are activated by noxious chemical, thermal or mechanical stimuli. The activated nociceptors convey information regarding the noxious stimuli to pain processing centers in the spinal cord and brain (Fields, H., Pain (McGraw-Hill, N.Y., 1987). Nociceptors are characterized in part, by their sensitivity to vanilloids (i.e., chemicals containing vanillyl groups), such as, for example, capsaicin, the main pungent ingredient in capsaicin peppers. In mammals, exposure of nociceptor terminals to capsaicin leads to excitation of the neuron and the consequent perception of pain and local release of inflammatory mediators. Prolonged exposure of nociceptor terminals to capsaicin leads to the desensitization of these neurons to capsaicin and other noxious stimuli (Szolcsanyi, Y., in Capsaicin and the Study of Pain (ed. Wood J.) 255-272 (Academic, London, 1993). This phenomenon of desensitization has led to the use of capsaicin as an analgesic agent in the treatment of painful disorders ranging from viral and diabetic neuropathies to rheumatoid arthritis (Campbell, E., in Capsaicin and the Study of Pain (ed. Wood J.) 255-272 (Academic, London, 1993; Szallasi et al., Pain 68:195208 (1996)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with chronic pain, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “chronic pain” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on chronic pain. You can also use this procedure to view pending patent applications concerning chronic pain. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
201
CHAPTER 7. BOOKS ON CHRONIC PAIN Overview This chapter provides bibliographic book references relating to chronic pain. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on chronic pain include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “chronic pain” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on chronic pain: •
Coping with Chronic Pain. A Guide to Patient Self-Management Source: New York, NY: Guilford Press. 1990. 240 p. Contact: Available from Guilford Press. 72 Spring Street, New York, NY 10012. (212) 431-9800. PRICE: $30 plus $2.50 shipping. Summary: This book describes the self-management approach to treating patients with refractory chronic pain, based on the experience of an outpatient pain clinic that evaluates and treats clients in an intensive 21-day patient program. Biomedical and biopsychosocial models are discussed in detail with respect to how each: presumes pain mechanisms operate; views the phenomenoloy of pain experience; and determines appropriate interventions. Of concern is how a person appraises, reacts to, and copes with the problem and its treatment. Evaluation and preparation of the patient for selfmanagement training includes reciprocal interactions among physical sensations, cognitive factors, emotional responses, overt behavior, and socioenvironmental features.
202 Chronic Pain
Essential targets for change such as dysfunctional action tendencies, perceptions of uncontrollability, and self-focused attention are determined. Chapters cover the critical issues of physical activity reconditioning, attentional refocusing, a non-narcotic preventive approach for acute pain episodes, and managing stress and depression. The administrative, budgetary, and staff issues for operating a comprehensive pain center are also addressed. 197 references. •
Poetry of Pain: Poems of Truth, Acceptance and Hope for Those Who Suffer Chronic Pain Source: Lynnwood, WA: Simply Books. 1996. 63 p. Contact: Available from Simply Books, P.O. Box 2205, Lynnwood, WA 98036. (206) 7451895. (206) 787-4135 (fax). PRICE: $9.95 in the U.S., $14.95 in Canada. Summary: This book for health professionals, the general public, and individuals with chronic pain uses poetry to present a personal account of the experience of chronic pain. The poems convey the emotions of chronic pain sufferers and the phases of pain they experience, including frustration, anger, depression, acknowledgement, acceptance, and hope. This compilation of poems offers reassurance to chronic pain sufferers and helps family members and health care professionals understand the reality of their pain.
•
Essential Arthritis Cookbook: Kitchen Basics for People with Arthritis, Fibromyalgia and Other Chronic Pain and Fatigue Source: Mankato, MN: Appletree Press, Inc. 1995. 286 p. Contact: Available from Appletree Press, Inc. 151 Good Counsel Drive, Suite 125, Mankato, MN 56001. (800) 322-5679 or (507) 345-4848. Fax (507) 345-3002. PRICE: $24.95 plus shipping and handling. ISBN 0962047163. Summary: This cookbook for people with arthritis, fibromyalgia, and other chronic pain and fatigue explains how nutrition affects arthritis and other musculoskeletal diseases and uses this information to provide guidelines and recipes for good health. Chapters cover topics such as the relationship between diet and arthritis; the impact of diet on the reduction of pain, swelling, and stiffness; and the effect of various arthritis medications on vitamin and mineral levels in the body. Other chapters offer suggestions for developing an energy-saving plan, making cooking more relaxing, protecting joints from damaging forces, selecting appropriate tools, and planning meals. In addition, the book provides more than 120 recipes in the categories of appetizers, soups, salads, main dishes, vegetables, side dishes, breads, and desserts. The recipes are easy to prepare and require few ingredients and minimal cleanup. Appendixes offer suggestions for making eating easier for people whose illness or condition has made eating difficult, and provide advice for using convenience foods. 14 figures. 25 tables. 7 references.
•
The Chronic Pain Control Workbook. A Step-by-Step Guide for Coping With and Overcoming Your Pain Source: Oakland, CA: New Harbinger Publications, Inc. 1991. 212 p. Contact: Available from New Harbinger Publications, Inc. 5674 Shattuck Avenue, Oakland, CA 94609. (800) 748-6273. PRICE: $13.95 (18.95 Canada) plus $3.80 for shipping and handling. ISBN: 0934986452. Summary: This text is designed for the chronic pain sufferer, but offers health professionals at all levels a rational approach to understanding chronic pain and its
Books
203
management. Throughout, the authors emphasize that the patient must take responsibility for carrying out his or her own treatment, a responsibility that can be accomplished by setting realistic goals and learning specific skills. Seventeen chapters cover learning to cope, theories of pain, exercise, pain and basic stress management, advanced stress management techniques, psychological techniques for managing chronic pain, dealing with others, medications for chronic pain, back and neck pain, headaches, temporomandibular disorders, arthritis, irritable bowel syndrome, neuralgias, vocational rehabilitation and chronic pain, pain clinics and support groups, and relapse and recovery. One appendix details how to make a personalized relaxation tape.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “chronic pain” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “chronic pain” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “chronic pain” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
60 Second Chronic Pain Relief: The Quickest Way to Soften the Throb, Cool the Burn, Ease the Ache (60 Second Series , No 3) by Peter G. Lehndorff, Brian Tarcy (Contributor) (1996); ISBN: 0882821512; http://www.amazon.com/exec/obidos/ASIN/0882821512/icongroupinterna
•
A Chronic Pain Management Manual: A guide for those who suffer and those who treat pain by Philip Fisher (2002); ISBN: 0595226779; http://www.amazon.com/exec/obidos/ASIN/0595226779/icongroupinterna
•
Above and Beyond: 365 Meditations for Transcending Chronic Pain and Illness by J. S. Dorian, P. S. Dorian (1996); ISBN: 0452276268; http://www.amazon.com/exec/obidos/ASIN/0452276268/icongroupinterna
•
Assessing Chronic Pain (1989); ISBN: 354096942X; http://www.amazon.com/exec/obidos/ASIN/354096942X/icongroupinterna
•
Assessing Chronic Pain: A Multidisicplinary Clinic Handbook (Contributions to Psychology and Medicine) by Frederick D. Brown (Editor), Paul Marc Camic (1989); ISBN: 038796942X; http://www.amazon.com/exec/obidos/ASIN/038796942X/icongroupinterna
•
Assessment of Chronic Pain Patients With the Mmpi-2 (Mmpi-2 Monographs, Vol 2) by Laura S. Keller, James N. Butcher (Contributor) (1991); ISBN: 0816618615; http://www.amazon.com/exec/obidos/ASIN/0816618615/icongroupinterna
•
Back in Balance: A Chronic Pain Workbook by Barbara J. Headley, Jodee Kulp (Illustrator); ISBN: 0929538021; http://www.amazon.com/exec/obidos/ASIN/0929538021/icongroupinterna
204 Chronic Pain
•
Behavioral Methods for Chronic Pain and Illness by Wilbert Evans, Fordyce; ISBN: 0801616212; http://www.amazon.com/exec/obidos/ASIN/0801616212/icongroupinterna
•
Biocultural Dimensions of Chronic Pain: Implications for Treatment of Multi-Ethnic Populations (Suny Series in Medical Anthropology) by Maryann S. Bates (1996); ISBN: 0791427358; http://www.amazon.com/exec/obidos/ASIN/0791427358/icongroupinterna
•
Camp Pain: Talking With Chronic Pain Patients by Jean E. Jackson (1999); ISBN: 0812217152; http://www.amazon.com/exec/obidos/ASIN/0812217152/icongroupinterna
•
Childhood Abuse and Chronic Pain: A Curious Relationship? by Michael R. Bond, Ranjan Roy; ISBN: 0802007392; http://www.amazon.com/exec/obidos/ASIN/0802007392/icongroupinterna
•
Chronic Pain by Troels S. Jensen, et al (2002); ISBN: 0340731540; http://www.amazon.com/exec/obidos/ASIN/0340731540/icongroupinterna
•
Chronic Pain by Joyce Engle (2001); ISBN: 1569001324; http://www.amazon.com/exec/obidos/ASIN/1569001324/icongroupinterna
•
Chronic Pain by Thomas W. Miller (Editor) (1990); ISBN: 0823608514; http://www.amazon.com/exec/obidos/ASIN/0823608514/icongroupinterna
•
Chronic Pain (1990); ISBN: 068307394X; http://www.amazon.com/exec/obidos/ASIN/068307394X/icongroupinterna
•
Chronic Pain by Randal D. France, K. Ranga Rama Krishnan (Editor) (1988); ISBN: 0880482060; http://www.amazon.com/exec/obidos/ASIN/0880482060/icongroupinterna
•
Chronic Pain by Anthony Bellissimo (Author), Eldon Tunks (Author) (1984); ISBN: 0275914224; http://www.amazon.com/exec/obidos/ASIN/0275914224/icongroupinterna
•
Chronic Pain (Natural Way of Healing) by Natural Medicine Collective, et al (1995); ISBN: 0440216583; http://www.amazon.com/exec/obidos/ASIN/0440216583/icongroupinterna
•
Chronic Pain (Sound Techniques for Healing) by Robert Friedman, et al (1993); ISBN: 1881451224; http://www.amazon.com/exec/obidos/ASIN/1881451224/icongroupinterna
•
Chronic Pain Control Workbook by Kimeron N. Hardin, et al (1997); ISBN: 1567312101; http://www.amazon.com/exec/obidos/ASIN/1567312101/icongroupinterna
•
Chronic Pain Evaluation, A Valid, Standardized Assessment Instrument by Karen S. Rucker (2001); ISBN: 0750671211; http://www.amazon.com/exec/obidos/ASIN/0750671211/icongroupinterna
•
Chronic Pain in Later Life: A Selectively Annotated Bibliography (Bibliographies and Indexes in Gerontology) by Karen A. Roberto (Author), Deborah T. Gold (Author); ISBN: 0313310998; http://www.amazon.com/exec/obidos/ASIN/0313310998/icongroupinterna
•
Chronic Pain in Old Age: An Integrated Biopsychosocial Perspective by Ranjan Roy (Editor) (1995); ISBN: 0802028594; http://www.amazon.com/exec/obidos/ASIN/0802028594/icongroupinterna
Books
205
•
Chronic Pain: A Handbook for Nurses by Marcus Munafo (Editor), Jacquie Trim (2000); ISBN: 0750641207; http://www.amazon.com/exec/obidos/ASIN/0750641207/icongroupinterna
•
Chronic Pain: Assessment, Diagnosis, and Management by Michael S., Md., Ph.D. Margoles (Editor), Richard, Phd. Weiner (Editor); ISBN: 1574441035; http://www.amazon.com/exec/obidos/ASIN/1574441035/icongroupinterna
•
Chronic Pain: Biomedical and Spiritual Approaches by Harold G., Md. Koenig (2003); ISBN: 0789016397; http://www.amazon.com/exec/obidos/ASIN/0789016397/icongroupinterna
•
Chronic Pain: Finding a Life Worth Living by Jan Nyberg (Editor); ISBN: 0533108683; http://www.amazon.com/exec/obidos/ASIN/0533108683/icongroupinterna
•
Chronic Pain: Taking Command of Our Healing!: Understanding the Emotional Trauma Underlying Chronic Pain by Wm. R. B. Anderson, et al (1995); ISBN: 0964297906; http://www.amazon.com/exec/obidos/ASIN/0964297906/icongroupinterna
•
Chronic Pain: The Occupational Therapist's Perspective by Strong (1996); ISBN: 0443052514; http://www.amazon.com/exec/obidos/ASIN/0443052514/icongroupinterna
•
Chronic Poetry: A Daily Journey For People Living With Chronic Pain: A Collection of Poems by Jeanne Johnson (2002); ISBN: 1588987256; http://www.amazon.com/exec/obidos/ASIN/1588987256/icongroupinterna
•
Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms by Harold Merskey, Nikolai Bogduk (1994); ISBN: 0931092051; http://www.amazon.com/exec/obidos/ASIN/0931092051/icongroupinterna
•
Cognitive Therapy With Chronic Pain Patients by Carrie Ph.D. Winterowd, et al (2003); ISBN: 0826145957; http://www.amazon.com/exec/obidos/ASIN/0826145957/icongroupinterna
•
Conquering Chronic Pain After Injury by William Simon, et al (2002); ISBN: 1583331409; http://www.amazon.com/exec/obidos/ASIN/1583331409/icongroupinterna
•
Contemporary Issues in Chronic Pain (Current Management of Pain, 9) by Winston C.V. Parris (Editor) (1991); ISBN: 0792311825; http://www.amazon.com/exec/obidos/ASIN/0792311825/icongroupinterna
•
Diagnosis and Nonsurgical Management of Chronic Pain by Nelson H. Hendler; ISBN: 0890042896; http://www.amazon.com/exec/obidos/ASIN/0890042896/icongroupinterna
•
Dlpa to End Chronic Pain and Depression by Arnold Fox, et al; ISBN: 0671631209; http://www.amazon.com/exec/obidos/ASIN/0671631209/icongroupinterna
•
Doctor's Guide to Chronic Pain: The Newest, Quickest, and Most Effective Ways to Find Relief by Richard Laliberte (2004); ISBN: 0762104686; http://www.amazon.com/exec/obidos/ASIN/0762104686/icongroupinterna
•
Evaluation and Treatment of Chronic Pain (1992); ISBN: 080670151X; http://www.amazon.com/exec/obidos/ASIN/080670151X/icongroupinterna
206 Chronic Pain
•
Evaluation and Treatment of Chronic Pain by Gerald M. Aronoff (Editor) (1992); ISBN: 0683002619; http://www.amazon.com/exec/obidos/ASIN/0683002619/icongroupinterna
•
Exercise for the Chronic Pain Patient by Mark Muse, et al (1985); ISBN: 0932392202; http://www.amazon.com/exec/obidos/ASIN/0932392202/icongroupinterna
•
Freedom from Chronic Pain : The Breakthrough Method of Pain Relief Based on the New York Pain Treatment Program at Lenox Hill Hospital by Norman J. Marcus (Author), Jean S. Arbeiter (Author) (1995); ISBN: 0671511653; http://www.amazon.com/exec/obidos/ASIN/0671511653/icongroupinterna
•
FROM LESION TO METAPHOR: Chronic Pain in British, French and German Medical Writings, 1800-1914. (Clio Medica/The Wellcome Institute Series in the History of Medicine 58) by Andrew HODGKISS; ISBN: 9042008318; http://www.amazon.com/exec/obidos/ASIN/9042008318/icongroupinterna
•
Good Days Bad Days: Living With Chronic Pain and Illness by Linda Raney Wright (1991); ISBN: 0840733445; http://www.amazon.com/exec/obidos/ASIN/0840733445/icongroupinterna
•
Group Wellness Programs for Chronic Pain and Disease Management by Carolyn A. McManus (2003); ISBN: 0750673974; http://www.amazon.com/exec/obidos/ASIN/0750673974/icongroupinterna
•
Gunn Approach to the Treatment of Chronic Pain: Intramuscular Stimulation for Myofascial Pain of Radiculopathic Origin by Patrick D. Wall, Christine Gunn; ISBN: 0443054223; http://www.amazon.com/exec/obidos/ASIN/0443054223/icongroupinterna
•
Handbook of Chronic Pain Management by C. David Tollison (Editor); ISBN: 068308335X; http://www.amazon.com/exec/obidos/ASIN/068308335X/icongroupinterna
•
Help Yourself to Chronic Pain Relief: The Patient's Point of View by Gloria J. Epstein (1981); ISBN: 0960579206; http://www.amazon.com/exec/obidos/ASIN/0960579206/icongroupinterna
•
Journey With Pain: Creative Strategies for Coping With Chronic Pain by Ronald L. Barozzi (1997); ISBN: 1560723270; http://www.amazon.com/exec/obidos/ASIN/1560723270/icongroupinterna
•
Key Topics in Chronic Pain by K. M. Grady, et al (1997); ISBN: 1859960766; http://www.amazon.com/exec/obidos/ASIN/1859960766/icongroupinterna
•
Learning to Master Your Chronic Pain by Robert N. Jamison (1996); ISBN: 1568870191; http://www.amazon.com/exec/obidos/ASIN/1568870191/icongroupinterna
•
Living With Chronic Pain (Master's Touch Series) by Concordia Publishing Staff, Concordia Publishing House (1994); ISBN: 0570094356; http://www.amazon.com/exec/obidos/ASIN/0570094356/icongroupinterna
•
Living With Chronic Pain: One Day at a Time by Mark A. Zabawa, Maggie Rose (Illustrator); ISBN: 0963735306; http://www.amazon.com/exec/obidos/ASIN/0963735306/icongroupinterna
•
Malic Acid & Magnesium for Fibromyalgia & Chronic Pain Syndrome by Billie J. Sahley (1999); ISBN: 1889391158; http://www.amazon.com/exec/obidos/ASIN/1889391158/icongroupinterna
Books
207
•
Malic Acid and Magnesium for Fibromyalgia and Chronic Pain Syndrome by Billie Jay Sahley (1994); ISBN: 0962591459; http://www.amazon.com/exec/obidos/ASIN/0962591459/icongroupinterna
•
Management of Patients With Chronic Pain by Steven F. Brena; ISBN: 0893351652; http://www.amazon.com/exec/obidos/ASIN/0893351652/icongroupinterna
•
Managing Chronic Pain: A Patient's Guide by C. David Tollison (1982); ISBN: 0806955716; http://www.amazon.com/exec/obidos/ASIN/0806955716/icongroupinterna
•
Mastering Chronic Pain: A Professional's Guide to Behavioral Treatment by Robert N. Jamison (1996); ISBN: 1568870183; http://www.amazon.com/exec/obidos/ASIN/1568870183/icongroupinterna
•
Mastering Pain: A Twelve-Step Program for Coping With Chronic Pain by Richard A. Sternbach; ISBN: 0345354281; http://www.amazon.com/exec/obidos/ASIN/0345354281/icongroupinterna
•
Mayo Clinic on Chronic Pain by Jeffrey Rome (Editor), et al (2002); ISBN: 1893005275; http://www.amazon.com/exec/obidos/ASIN/1893005275/icongroupinterna
•
Medical Care and Risks of Dysfunctional Chronic Pain: Abstract, Executive Summary, Final Report and Appendices A-C by Michael Van Korff (1996); ISBN: 0788145053; http://www.amazon.com/exec/obidos/ASIN/0788145053/icongroupinterna
•
Multidimensional Assessment of People With Chronic Pain: A Critical Appraisal of the Person, Environment, Occupation Model (Uppsala Dissertations from the Faculty of Medicine, 6) by Marie-Louise Schult (2002); ISBN: 9155453678; http://www.amazon.com/exec/obidos/ASIN/9155453678/icongroupinterna
•
Multimethod Assessment of Chronic Pain (1987); ISBN: 0080323774; http://www.amazon.com/exec/obidos/ASIN/0080323774/icongroupinterna
•
Nature's Pain Killers: Proven New Alternative and Nutritional Therapies for Chronic Pain Relief by Carl Germano, William Cabot (1999); ISBN: 1575665026; http://www.amazon.com/exec/obidos/ASIN/1575665026/icongroupinterna
•
Neurosurgical and Medical Management of Pain: Trigeminal Neuralgia, Chronic Pain, and Cancer Pain (Topics in Neurosurgery; Tins 3) by Ronald Brisman (Editor) (1989); ISBN: 0898384052; http://www.amazon.com/exec/obidos/ASIN/0898384052/icongroupinterna
•
New Concepts in Craniomandibular and Chronic Pain Management by Harold Gelb (Editor) (1994); ISBN: 0723420416; http://www.amazon.com/exec/obidos/ASIN/0723420416/icongroupinterna
•
New Concepts in Craniomandibular and Chronic Pain Management (1994); ISBN: 0912791500; http://www.amazon.com/exec/obidos/ASIN/0912791500/icongroupinterna
•
Older Women With Chronic Pain by Karen A. Roberto (Editor) (1994); ISBN: 1560247061; http://www.amazon.com/exec/obidos/ASIN/1560247061/icongroupinterna
•
Pain Assessment Instruments for Chronic Pain Evaluation a Valid Standardized Assessment Instrument by Karen S. Rucker (2000); ISBN: 075067301X; http://www.amazon.com/exec/obidos/ASIN/075067301X/icongroupinterna
208 Chronic Pain
•
Pain Cure: Proven Medical Program That Helps End Your Chronic Pain by Dharma Singh M.D. Khalsa (Author) (2000); ISBN: 0446675865; http://www.amazon.com/exec/obidos/ASIN/0446675865/icongroupinterna
•
Pain Free for Women: The Revolutionary Program for Ending Chronic Pain by Pete Egoscue, Roger Gittines (Contributor) (2002); ISBN: 0553801058; http://www.amazon.com/exec/obidos/ASIN/0553801058/icongroupinterna
•
Pain-Free with Magnet Therapy: Discover how Magnets can Help Relieve Arthritis, Sports Injuries, Fibromyalgia, and Chronic Pain by Lara Owen; ISBN: 0761520864; http://www.amazon.com/exec/obidos/ASIN/0761520864/icongroupinterna
•
Patient or Person: Living With Chronic Pain by Penney Cowan, Edward Covington (Designer) (1992); ISBN: 0898761867; http://www.amazon.com/exec/obidos/ASIN/0898761867/icongroupinterna
•
Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues (Progress in Pain Research&Therapy Ser) by Fields (Editor) (1994); ISBN: 0931092043; http://www.amazon.com/exec/obidos/ASIN/0931092043/icongroupinterna
•
Physical Medicine and Rehabilitation: Chronic Pain (State of the Art Reviews, Vol 5/No 1) by N. Walsh (1991); ISBN: 1560530316; http://www.amazon.com/exec/obidos/ASIN/1560530316/icongroupinterna
•
Presurgical Psychological Screening in Chronic Pain Syndromes: A Guide for the Behavioral Health Practitioner by Andrew R. Block (1996); ISBN: 0805824073; http://www.amazon.com/exec/obidos/ASIN/0805824073/icongroupinterna
•
Prolo Your Pain Away: Curing Chronic Pain with Prolothereapy by FC&A Publishing (2001); ISBN: 189095750X; http://www.amazon.com/exec/obidos/ASIN/189095750X/icongroupinterna
•
Psychiatric Management of Chronic Pain, Patient (5 Copies) by Philips (1996); ISBN: 2015773002; http://www.amazon.com/exec/obidos/ASIN/2015773002/icongroupinterna
•
Recrafting a Life: Solutions for Chronic Pain and Illness by Charlie Johnson, et al (2002); ISBN: 1583913564; http://www.amazon.com/exec/obidos/ASIN/1583913564/icongroupinterna
•
Scientific Foundations of Chronic Pain Therapy by Rajesh Munglani (Editor); ISBN: 1900151839; http://www.amazon.com/exec/obidos/ASIN/1900151839/icongroupinterna
•
Silent Waves: Theory and Practice of Lymph Drainage Therapy, with Applications of Lymphedema, Chronic Pain and Inflammation by Bruno Chikly (2001); ISBN: 0970053053; http://www.amazon.com/exec/obidos/ASIN/0970053053/icongroupinterna
•
Studies on Dextropropoxyphene: With Special Reference to Dependence Among Chronic Pain Patients, Classification of the Manner of Death in Fatal Poisoning, and Characteristics of the (Comprehensive Summaries of Uppsala Dissertations, 933) by Birgitta Jonasson (2000); ISBN: 9155447295; http://www.amazon.com/exec/obidos/ASIN/9155447295/icongroupinterna
•
Sustained-release Opioids in Special Populations (New Directions in Chronic Pain) by Bruce Nicholson (2003); ISBN: 1853155330; http://www.amazon.com/exec/obidos/ASIN/1853155330/icongroupinterna
Books
209
•
The Chronic Pain Control Workbook: A Step-By-Step Guide for Coping With and Overcoming Pain by Ellen Mohr Catalano, et al (1996); ISBN: 1572240504; http://www.amazon.com/exec/obidos/ASIN/1572240504/icongroupinterna
•
The Chronic Pain Patient: Evaluation and Management (Pain and Headache, Vol 7) by Philip L. Gildenberg, R. A. Devaul (Editor) (1984); ISBN: 3805539118; http://www.amazon.com/exec/obidos/ASIN/3805539118/icongroupinterna
•
The Chronic Pain Solution : Your Personal Path to Pain Relief by James N. Dillard (Author) (2003); ISBN: 0553381113; http://www.amazon.com/exec/obidos/ASIN/0553381113/icongroupinterna
•
The Family and Chronic Pain by Ranjan Roy (Editor) (1986); ISBN: 0898853133; http://www.amazon.com/exec/obidos/ASIN/0898853133/icongroupinterna
•
The Management of Chronic Pain by Andrew Diamond, Stephen Coniam (Contributor); ISBN: 0192626957; http://www.amazon.com/exec/obidos/ASIN/0192626957/icongroupinterna
•
The Natural Way of Healing Chronic Pain by Natural Medicine Collective, Medicine Collective Natural (1995); ISBN: 0440613639; http://www.amazon.com/exec/obidos/ASIN/0440613639/icongroupinterna
•
The Rise Response: Illness, Wellness, and Spirituality: A Proven Program of Relief for People Coping With Cancer, Hiv, Chronic Pain, and Tension by Tim Flinders, et al (1994); ISBN: 0824513940; http://www.amazon.com/exec/obidos/ASIN/0824513940/icongroupinterna
•
The Social Context of the Chronic Pain Sufferer by Ranjan Roy (1992); ISBN: 0802028608; http://www.amazon.com/exec/obidos/ASIN/0802028608/icongroupinterna
•
The Truth About Chronic Pain: Patients and Professionals on How to Face It, Understand It, Overcome It by Arthur Rosenfeld, Isadore Rosenfeld (Foreword) (2003); ISBN: 0465071384; http://www.amazon.com/exec/obidos/ASIN/0465071384/icongroupinterna
•
The Ultimate Guide to Sex and Disability: For All of Us Who Live with Disabilities, Chronic Pain and Illness by Cory Silverburg, et al (2003); ISBN: 1573441767; http://www.amazon.com/exec/obidos/ASIN/1573441767/icongroupinterna
•
Transforming Your Chronic Pain by Jeff Kane (1992); ISBN: 1879237296; http://www.amazon.com/exec/obidos/ASIN/1879237296/icongroupinterna
•
Treatment of Chronic Pain by P.A. Van Zwieten, et al (1990); ISBN: 3718650266; http://www.amazon.com/exec/obidos/ASIN/3718650266/icongroupinterna
•
Understanding Chronic Pain by Angela J., Ph.D. Koestler, Ann, M.D. Myers; ISBN: 1578064406; http://www.amazon.com/exec/obidos/ASIN/1578064406/icongroupinterna
•
Validate Your Pain! Exposing the Chronic Pain Cover-Up by Alan F. Chino, Corinne D. Davis (2002); ISBN: 0970844492; http://www.amazon.com/exec/obidos/ASIN/0970844492/icongroupinterna
•
V-Antipsychotic Treatments for the Chronic Pain with Psychosis by David Picker (1999); ISBN: 0805833161; http://www.amazon.com/exec/obidos/ASIN/0805833161/icongroupinterna
210 Chronic Pain
•
When Your Pain Flares Up: Easy, Proven Techniques for Managing Chronic Pain by Fairview Press (2002); ISBN: 1577491203; http://www.amazon.com/exec/obidos/ASIN/1577491203/icongroupinterna
•
Winning With Chronic Pain: A Complete Program for Health and Well-Being (Consumer Health Library) by Harris H. McIlwain (Editor), et al (1994); ISBN: 0879758783; http://www.amazon.com/exec/obidos/ASIN/0879758783/icongroupinterna
•
Yet I Will Praise Him: Devotions of Praise Through Chronic Pain by Cindy R. Nelson (2001); ISBN: 0962118575; http://www.amazon.com/exec/obidos/ASIN/0962118575/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “chronic pain” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Characteristics determining success or failure in management of patients with chronic pain Author: Maruta, Toshihiko.; Year: 1976; [Minneapolis: s.n.], 1976
•
Chronic pain Author: Chapman, C. Richard.; Year: 1988; [Kalamazoo, Mich.]: Upjohn, c1985
•
Chronic pain: America's hidden epidemic Author: Brena, Steven F.,; Year: 1978; New York: Atheneum/SMI, 1978; ISBN: 0689108745 http://www.amazon.com/exec/obidos/ASIN/0689108745/icongroupinterna
•
Chronic pain: further observations from City of Hope National Medical Center Author: Crue, Benjamin L. (Benjamin Lane),; Year: 1979; New York: SP Medical and Scientific Books Division of Spectrum Publications, c1979
•
Chronic pain: its social dimensions Author: Kotarba, Joseph A.; Year: 1982; Beverly Hills: Sage Publications, c1983; ISBN: 0803918801 http://www.amazon.com/exec/obidos/ASIN/0803918801/icongroupinterna
•
Chronic pain: social and medical aspects: inaugural lecture delivered in the University of Natal, Durban, 2 June 1982 Author: Brock-Utne, J. G.; Year: 1983; Pietermaritzburg: University of Natal Press, 1982; ISBN: 0869803239
•
Chronic pain: the endemic disease of an industrial society: proceedings of the National Pain Seminar, San Francisco, California, March 19 to 21, 1980.; Year: 1980; [Washington, D.C.]: U.S. G.P.O., 1980
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
Books
211
•
Chronic pain: the psychotherapeutic spectrum Author: Bellissimo, Anthony.; Year: 1985; New York: Praeger, 1984; ISBN: 0030635047 http://www.amazon.com/exec/obidos/ASIN/0030635047/icongroupinterna
•
Chronic pain primer Author: Pawl, Ronald Phillip,; Year: 1979; Chicago: Year Book Medical Publishers, c1979; ISBN: 0815166508 http://www.amazon.com/exec/obidos/ASIN/0815166508/icongroupinterna
•
Coping with chronic pain Author: Hendler, Nelson H.,; Year: 1979; New York: Potter, c1979; ISBN: 0517534401 http://www.amazon.com/exec/obidos/ASIN/0517534401/icongroupinterna
•
Current concepts in the management of chronic pain: a Post-doctoral Pain Symposium, University of Delaware Author: LeRoy, Pierre L.,; Year: 1977; New York: Stratton Intercontinental Medical Book Corp., c1977; ISBN: 0883720914 http://www.amazon.com/exec/obidos/ASIN/0883720914/icongroupinterna
•
Diagnosis and treatment of chronic pain Author: Hendler, Nelson H.,; Year: 1981; Boston: Wright-PSG, 1982; ISBN: 0723670110 http://www.amazon.com/exec/obidos/ASIN/0723670110/icongroupinterna
•
Killing pain without prescription: a new and simple way to free yourself from headache, backache, and other sources of chronic pain Author: Gelb, Harold,; Year: 1980; New York: Harper; Row, c1980; ISBN: 0060114835 http://www.amazon.com/exec/obidos/ASIN/0060114835/icongroupinterna
•
Managing chronic pain: a patient's guide Author: Tollison, C. David,; Year: 1982; New York: Sterling Pub. Co., c1982; ISBN: 0806955708 http://www.amazon.com/exec/obidos/ASIN/0806955708/icongroupinterna
•
New approaches to treatment of chronic pain: a review of multidisciplinary pain clinics and pain centers Author: Ng, Lorenz K. Y.; Year: 1983; Rockville, Md.: Dept. of Health and Human Services, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute on Drug Abuse, Division of Research; Washington, D. C.: For sale by the Supt. of Docs.,U.S. G.P.O., 1981
•
Osteopuncture: relief from strong and chronic pain Author: Lowenkopf, Anne N.; Year: 1976; Santa Barbara, Calif.: Medical Arts Press, c1976
•
The care of patients with severe chronic pain in terminal illness: literature search. Author: Kenton, Charlotte.; Year: 1984; [S.l.]: American Medical Association and the United States Public Health Service, 1983
•
The chronic pain control workbook: a step-by-step guide for coping with and overcoming your pain Author: Catalano, Ellen Mohr.; Year: 1982; Oakland, CA: New Harbinger Publications, c1987; ISBN: 0934986452
•
The control of chronic pain Author: Lipton, Sampson.; Year: 1979; London: Arnold; Chicago: Distributed by Year Book Medical, 1979; ISBN: 0815155042 http://www.amazon.com/exec/obidos/ASIN/0815155042/icongroupinterna
•
The psychological management of chronic pain: a treatment manual Author: Philips, Clare.; Year: 1989; New York: Springer Pub. Co., c1988; ISBN: 0826161103 http://www.amazon.com/exec/obidos/ASIN/0826161103/icongroupinterna
•
The treatment of chronic pain. Author: Hart, F. Dudley (Francis Dudley); Year: 1975; [Lancaster] Medical and Technical Pub. Co. [c1974]; ISBN: 0852000820 http://www.amazon.com/exec/obidos/ASIN/0852000820/icongroupinterna
•
Vibratory stimulation for the alleviation of chronic pain Author: Lundeberg, Thomas C. M.; Year: 1974; Stockholm: [s.n.], 1983
212 Chronic Pain
Chapters on Chronic Pain In order to find chapters that specifically relate to chronic pain, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and chronic pain using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “chronic pain” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on chronic pain: •
Pathophysiology of Severe Tinnitus and Chronic Pain Source: in Hazell, J., ed. Proceedings of the Sixth International Tinnitus Seminar. London, England: Tinnitus and Hyperacusis Centre. 1999. p. 26-31. Contact: Available from Tinnitus and Hyperacusis Centre. 32 Devonshire Place, London, W1N 1PE, United Kingdom. Fax 44 + (0) 207 486 2218. E-mail:
[email protected]. Website: www.tinnitus.org. PRICE: Contact publisher for price. ISBN: 0953695700. Also available on CD-ROM. Summary: This article on the pathophysiology of severe tinnitus and chronic pain is from a lengthy document that reprints the proceedings of the Sixth International Tinnitus Seminar, held in Cambridge, United Kingdom, in September 1999 and hosted by the British Society of Audiology. In this article, the author defines severe tinnitus as that which interferes with sleep, work, and social life. In most cases, severe tinnitus is believed to be caused by changes in the function of the central auditory nervous system. However, some forms are caused by changes in the function of the cochlea, as evidenced from the fact that severing the auditory nerve can relieve tinnitus in some individuals. Topics include a comparison of symptoms and signs of tinnitus and chronic pain, current hypotheses about the generation of pain and tinnitus, the generation of central tinnitus, and similarities with other hyperactive disorders. The author concludes that the changes in the function of the central nervous system that cause chronic pain and severe tinnitus are not associated with morphologic changes that can be detected by known imaging techniques, but the areas of the brain that are activated can be identified by functional imaging tests. Few electrophysiologic or behavioral tests are abnormal in individuals with chronic tinnitus and chronic pain, which complicates the diagnosis of tinnitus and the ability to monitor progress of treatment. The clinician mainly has to rely on the patients reported symptoms. 2 figures. 25 references.
213
CHAPTER 8. MULTIMEDIA ON CHRONIC PAIN Overview In this chapter, we show you how to keep current on multimedia sources of information on chronic pain. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on chronic pain is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “chronic pain” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “chronic pain” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on chronic pain: •
Chronic Pain Source: Princeton, NJ: Films for the Humanities and Sciences. 199x. (videocassette). Contact: Available from Films for the Humanities and Sciences. P. O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126; (609) 452-1128. PRICE: $149.00 for purchase; $75.00 for rental. Order Number TF-1805. Summary: This videotape explores the problem of chronic pain. The focus is on the approach of treating chronic pain as a disorder in its own right, and not as a by-product of some other illness or disorder. (AA-M).
214 Chronic Pain
Bibliography: Multimedia on Chronic Pain The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in chronic pain (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on chronic pain: •
Biofeedback in the management of chronic pain [videorecording] Source: a Hahnemann University and Videotech Associates Inc. production; Year: 1983; Format: Videorecording; [S.l.]: The Associates, c1983
•
Chronic pain Source: low back / American College of Surgeons; Year: 1980; Format: Sound recording; [Chicago]: The College, [1980]
•
Chronic pain [videorecording] Source: author, Manaachehr Khatami; Year: 1982; Format: Videorecording; Dallas, Tex.: MEDTV, the Dept. of Biomedical Communications, the University of Texas Health Science Center, [1982]
•
Chronic pain [videorecording]: management styles and results Source: an AREN production; [produced at the facilities of WQED/Pittsburgh by QED Enterprises, Inc.]; Year: 1985; Format: Videorecording; [Pittsburgh, Pa.]: AREN, c1985
•
Chronic pain control for oncology patients teleconference [videorecording] Source: presented by the Laurence A. Grossman Medical Learning Center, Saint Thomas Hospital; Year: 1988; Format: Videorecording; Nashville, Tenn.: The Hospital, c1988
•
Chronic pain evaluation [videorecording] Source: produced by Regional Learning Resources Service, Salt Lake City, Utah, in cooperation with Interwest Regional Medical Education Center for Rehabilitation Medicine Service; Year: 1985; Format: Videorecording; [Washington, D.C.]: Veterans Administration, 1985
•
Chronic pain in geriatrics [videorecording]: assessment Source: produced by Geriatric Video Productions, Inc; Year: 1998; Format: Videorecording; Shavertown, PA: Geriatric Video Productions, c1998
•
Chronic pain in geriatrics [videorecording]: management Source: produced by Geriatric Video Productions, Inc; Year: 1998; Format: Videorecording; Shavertown, PA: Geriatric Video Productions, c1998
•
Chronic pain in women [videorecording] Source: Office of Research Services, Medical Arts and Photography Branch; Year: 1998; Format: Videorecording; [Bethesda, Md.: National Institutes of Health, 1998]
•
Clinical case reviews [videorecording]: management of severe chronic pain Source: moderator, James G. Jones; faculty, Russell K. Portenoy, Patricia M. LoRusso, Mathew Lefkowitz; Year: 1996; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1996
•
Management of chronic pain [videorecording] Source: with members of the Pain Treatment Service, Columbia University College of Physicians and Surgeons-Presbyterian Medical Center, New York; Leonard Brand, Howard L. Rosner, Robert H. Dworkin; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986
•
Management of chronic pain [videorecording] Source: a joint production of. Audio Visual Center and Staff Education; Year: 1993; Format: Videorecording; Oakland, CA: Kaiser Foundation Health Plan, c1993
Multimedia 215
•
Office management of chronic pain [videorecording] Source: Burnell Brown, Jr; Year: 1983; Format: Videorecording; New York: Network for Continuing Medical Education, 1983
•
Pharmacologic management of chronic pain [videorecording] Source: a co-production of Multimedia Communications and Physician Education and Development; Year: 2002; Format: Videorecording; Oakland, CA: Kaiser Foundation Health Plan, c2002
•
Shingles [videorecording]: treating the chronic pain Source: a presentation of Films for the Humanities & Sciences; Year: 2000; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2000
•
The Chronic pain patient [sound recording] Source: Pain Resource Center; Year: 1983; Format: Sound recording; [S.l.]: S.R. Levitt, c1983
•
The Rehabilitation of the patient with chronic pain [videorecording] Source: a Hahnemann Medical College & Hospital and World Video Corp. production; Year: 1981; Format: Videorecording; [S.l.]: Analgesic CME Group, c1981
•
Treatment of chronic pain [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1981; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1981
217
CHAPTER 9. PERIODICALS AND NEWS ON CHRONIC PAIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover chronic pain.
News Services and Press Releases One of the simplest ways of tracking press releases on chronic pain is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “chronic pain” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to chronic pain. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “chronic pain” (or synonyms). The following was recently listed in this archive for chronic pain: •
Long-term opioid use for chronic pain does not usually impair cognitive function Source: Reuters Medical News Date: October 28, 2003
•
Chronic pain costs Europe 34 billion euros a year Source: Reuters Health eLine Date: October 09, 2003
218 Chronic Pain
•
Latino immigrants in US at high risk for PTSD and chronic pain Source: Reuters Medical News Date: August 05, 2003
•
Chronic pain linked to atrophic gray matter changes Source: Reuters Medical News Date: March 21, 2003
•
Chronic pain often untreated in nursing homes Source: Reuters Health eLine Date: February 17, 2003
•
Chronic pain undertreated in children: expert Source: Reuters Health eLine Date: January 28, 2003
•
New agent reduces nociception in animal models of chronic pain Source: Reuters Medical News Date: December 06, 2002
•
Compound relieves chronic pain in rats Source: Reuters Health eLine Date: December 03, 2002
•
Pilot study suggests most chronic pain patients have tinnitus Source: Reuters Medical News Date: September 26, 2002
•
Race identified as a factor in chronic pain experience in young patients Source: Reuters Medical News Date: March 19, 2002
•
Race may be factor in young patients' chronic pain Source: Reuters Health eLine Date: March 18, 2002
•
Intrathecal calcium channel blocker effective for severe chronic pain Source: Reuters Industry Breifing Date: March 18, 2002
•
Topiramate shows promise for treatment of neuropathy and chronic pain Source: Reuters Industry Breifing Date: February 08, 2002
•
Cannabis spray helps ease chronic pain Source: Reuters Medical News Date: September 05, 2001
•
Cannabis spray helps ease chronic pain: study Source: Reuters Health eLine Date: September 04, 2001
•
Transdermal fentanyl preferred over other opioids for chronic pain Source: Reuters Industry Breifing Date: August 22, 2001
•
Yoga may help those with chronic pain Source: Reuters Health eLine Date: August 21, 2001
Periodicals and News
•
FDA accepts Advanced Neuromodulation's PMA for chronic pain treatment Source: Reuters Industry Breifing Date: July 09, 2001
•
Cognitive impairment common in patients with chronic pain Source: Reuters Medical News Date: June 28, 2001
•
Preliminary data support use of microcurrent stimulation for chronic pain Source: Reuters Medical News Date: May 28, 2001
•
FDA approves Equitech's MedRelief stimulator for chronic pain Source: Reuters Industry Breifing Date: March 01, 2001
•
Transgenic 'smart' mice more sensitive to chronic pain Source: Reuters Industry Breifing Date: January 29, 2001
•
Transdermal fentanyl effective for AIDS-related chronic pain Source: Reuters Medical News Date: January 29, 2001
219
The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “chronic pain” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.
220 Chronic Pain
Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “chronic pain” (or synonyms). If you know the name of a company that is relevant to chronic pain, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “chronic pain” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “chronic pain” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on chronic pain: •
Chronic Pain and Disability of Whiplash May Be Prevented by Prompt Administration of a Drug Used in Spinal Cord Injury Source: Lifeline: The Newsletter of the National Chronic Pain Outreach Association. p. 15-16. Summer 1999. Contact: Available from National Chronic Pain Outreach Association. P.O. Box 274, Millboro, VA 24460. (540) 862-9437. Fax (540) 862-9485. E-mail:
[email protected]. Summary: This newsletter article for health professionals and people who have chronic pain reports on the use of a drug used in spinal cord injury to prevent chronic pain and disability of whiplash. Whiplash is an extension/flexion injury to the neck that frequently occurs from a rear hit motor vehicle accident. A study has found that methylprednisolone (MPS), a powerful synthetic corticosteroid, may help prevent chronic pain and other symptoms following whiplash. Patients participating in the study received either high-dose MPS or placebo. At 6 month followup there was a significant difference in prevalence of disabling symptoms between the treated and placebo groups. No one in the MPS group was still on sick leave, but four participants in the placebo group were still on sick leave and taking analgesics daily for neck and radiating pain in their arms. Early initiation of treatment with MPS is crucial because posttraumatic decrease in blood flow to the injury site results in decreased MPS uptake. Although high-dose MPS cannot be recommended for whiplash patients until additional studies are conducted, a single 30 milligram per kilogram dose of MPS is virtually without harmful effects.
Periodicals and News
•
221
Drug Therapy of Chronic Pain Source: Lifeline: The Newsletter of the National Chronic Pain Outreach Association. p. 6-8,10-12. Fall 1998. Contact: Available from National Chronic Pain Outreach Association. P.O. Box 274, Millboro, VA 24460. (540) 862-9437. Fax (540) 862-9485. E-mail:
[email protected]. Summary: This newsletter article provides health professionals and people who have chronic pain with information on the main classes of drugs used to treat pain. Medications are usually taken orally in the form of a pill, capsule, tablet, or liquid, but some may be delivered through creams, skin patches, inhalers, injections, spinal catheters, and rectal suppositories. The main drugs used to treat pain are the nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and a group referred to as adjuvant analgesics. NSAID classes include salicylates, propionic acids, acetic acids, fenamates, and oxicams. Opioid analgesics have long been an accepted therapeutic modality in the treatment of acute and chronic pain; however, concerns about dosage increases and addiction have lead to controversy over their use. Evidence indicates that these concerns are unfounded, so opioids are appropriate for pain management. Morphine and fentanyl are two opioid formulations uniquely made for management of chronic pain. Adjuvant analgesics are a mixed class of medications that may be used to provide additive analgesic effect and to counteract the side effects of more traditional analgesics. Adjuvant analgesics include tricyclic antidepressants, anticonvulsants, benzodiazepines, antihistamines, stimulants such as caffeine and dextroamphetamine, steroids, phenothiazines, oral local anesthetics, sympatholytics, sumatriptan, and topical capsaicin. The article discusses the rationale for selecting particular drugs over others, their mechanism of action, and their common side effects. 3 tables and 17 references.
Academic Periodicals covering Chronic Pain Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to chronic pain. In addition to these sources, you can search for articles covering chronic pain that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
223
CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for chronic pain. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with chronic pain. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
224 Chronic Pain
following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to chronic pain: Fentanyl •
Transdermal-Systemic - U.S. Brands: Duragesic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202702.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to chronic pain by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “chronic pain” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From
Researching Medications
225
there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for chronic pain: •
Morphine sulfate concentrate (preservative free) (trade name: Infumorph) http://www.rarediseases.org/nord/search/nodd_full?code=162
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
227
APPENDICES
229
APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
230 Chronic Pain
•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
Physician Resources
231
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
232 Chronic Pain
•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “chronic pain” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 31029 561 1031 161 30 32812
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “chronic pain” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
Physician Resources
233
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
20 Adapted 21
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
235
APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on chronic pain can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to chronic pain. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to chronic pain. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “chronic pain”:
236 Chronic Pain
•
Other guides Menstruation and Premenstrual Syndrome http://www.nlm.nih.gov/medlineplus/menstruationandpremenstrualsyndrome.ht l Mental Health http://www.nlm.nih.gov/medlineplus/mentalhealth.html Neck Disorders and Injuries http://www.nlm.nih.gov/medlineplus/neckdisordersandinjuries.html Peripheral Nerve Disorders http://www.nlm.nih.gov/medlineplus/peripheralnervedisorders.html Post-Traumatic Stress Disorder http://www.nlm.nih.gov/medlineplus/posttraumaticstressdisorder.html Reflex Sympathetic Dystrophy http://www.nlm.nih.gov/medlineplus/reflexsympatheticdystrophy.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on chronic pain. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Integration of Behavioral and Relaxation Approaches into the Treatment of Chronic Pain and Insomnia Source: Kensington, MD: NIH Consensus Program Information Center. October 1995. 38 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL:
[email protected]. PRICE: Free. Publication Number: D031. Summary: This consensus statement provides physicians with a responsible assessment of the integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia. After the introduction, the report answers five major research questions: (1) What behavioral and relaxation approaches are used for conditions such as chronic pain and insomnia? (2) How successful are these approaches? (3) How do
Patient Resources
237
these approaches work? (4) Are there barriers to the appropriate integration of these approaches into health care? and (5) What are the significant issues for future research and applications? The report ends with a list of experts who served as members of the technology assessment panel and planning committee. 86 references. •
About Living With Chronic Pain Source: South Deerfield, MA: Channing L. Bete Company, Inc. 1996. 15 p. Contact: Available from Channing L. Bete Company, Inc., South Deerfield, MA 01373. (800) 628-7733. Summary: This illustrated booklet for the general public focuses on living with chronic pain. Acute and chronic pain are defined. Methods of treating chronic pain are discussed, including medications, electric stimulation, nerve block, surgery, individual or group therapy, behavior modification, occupational therapy, physical therapy, relaxation and meditation, hypnosis, biofeed back, and acupuncture. Ways to live with pain are suggested, including accepting the pain, reducing stress, and staying healthy and active. In addition, some common myths about chronic pain are presented, and sources of information about chronic pain are provided.
•
Managing Your Chronic Pain Source: San Bruno, CA: StayWell Company. 1998. 16 p. Contact: Available from StayWell Company. 1100 Grundy Lane, San Bruno, CA 940663030. (800) 333-3032. Website: www.staywell.com. PRICE: Call or write for current pricing on single and bulk orders. Summary: This illustrated booklet provides people who have chronic pain with information on managing it. Short term pain tells a person that something is wrong, then it goes away. However, chronic pain is a constant pain that may not have a clear cause or else its cause cannot be removed. Chronic pain can be controlled by understanding pain, using professional care, and taking an active role. Chronic pain can lead to a chronic pain cycle. The less active a person becomes as a result of chronic pain, the weaker he or she becomes. This may lead to feelings of frustration and depression. When pain diminishes, a period of overexertion may occur, followed by a return of symptoms. This leads to a return to inactivity and a renewal of the cycle. A team of specialists may be needed to manage the needs of a person with chronic pain. The team will evaluate the medical, physical, work, and emotional needs of the patient and try to meet them in various ways. Treatment options include medications, transcutaneous electrical nerve stimulation, nerve blocks, and biofeedback. Self care is also an important part of pain management. The booklet provides suggestions on caring for one's body, emotions, and social needs. The booklet also includes questions readers can use to assess their chronic pain and identifies sources of information. The National Guideline Clearinghouse™
The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “chronic pain” (or synonyms). The following was recently posted:
238 Chronic Pain
•
Chronic pain management in the long-term care setting Source: American Medical Directors Association - Professional Association; 1999; 34 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2158&nbr=1384&a mp;string=chronic+AND+pain
•
Guideline for the management of acute and chronic pain in sickle cell disease Source: American Pain Society - Professional Association; 1999 August; 96 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2621&nbr=1847&a mp;string=chronic+AND+pain
•
VHA/DoD clinical practice guideline for the management of medically unexplained symptoms: chronic pain and fatigue Source: Department of Defense - Federal Government Agency [U.S.]; 2002 August; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3415&nbr=2641&a mp;string=chronic+AND+pain Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Chronic Pain Information Summary: A general overview of chronic pain that includes a description and information about treatment, prognosis and research. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3523
•
Hysterectomy: Know Your Options Summary: Answers to women's concerns about this medical procedure that is frequently recommended as a solution to relieve chronic pain and/or heavy bleeding that is caused by fibroids, endometriosis, and other Source: National Women's Health Resource Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2596
Patient Resources
•
239
Managing Chronic Pain Summary: healthfinder® — your guide to reliable health information health library just for you health care organizations search: go help | about healthfinder® Managing Chronic Source: American Occupational Therapy Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7340
•
Osteogenesis Imperfecta (OI) Issues: Pain Management Summary: Management strategies for acute and chronic pain resulting from multiple fractures, vertebral collapse, joint deformity, osteoarthritis, contractures, deformity/malalignment of limbs, and recurrent Source: Osteogenesis Imperfecta Foundation, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2231 The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to chronic pain. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
240 Chronic Pain
Associations and Chronic Pain The following is a list of associations that provide information on and resources relating to chronic pain: •
American Chronic Pain Association Telephone: (916) 632-0922 Toll-free: (800) 533-3231 Fax: (916) 632-3208 Email:
[email protected] Web Site: http://www.theacpa.org Background: The American Chronic Pain Association is a nonprofit self-help organization that provides assistance and hope to individuals with chronic pain. Established in 1980, the American Chronic Pain Association operates support groups throughout the United States and offers its members positive and constructive methods for dealing with chronic pain. Groups usually consist of approximately 10 members who learn useful techniques for pain management through discussion, mutual support, and informational exchanges. Educational materials produced by the American Chronic Pain Association include 'Help and Hope' pamphlets and brochures, guidelines for the selection of a pain unit, the 'American Chronic Pain Association Member Workbook,' tapes, and the 'American Chronic Pain Association Chronicle.'.
•
North American Chronic Pain Association of Canada Telephone: 905 793-5230 Toll-free: (800) 616-7246 Fax: (905) 793-8781 Email:
[email protected] Web Site: http://www3.sympatico.ca/nacpac Background: The North American Chronic Pain Association of Canada (NACPAC) is a nonprofit self-help organization dedicated to providing assistance and hope to individuals with chronic pain. NACPAC defines chronic pain as any frequent or continuous pain that has lasted more than a few months. This includes, but is not limited to, lower back pain, fibromyalgia, arthritis, headaches and migraines, and neck and shoulder pain. NACPAC was established in 1986 and currently consists of approximately 1,000 members. NACPAC brings together affected individuals through mutual support groups operating throughout Canada. Where no group exists, NACPAC provides materials and guidance on how to establish a support group. Members are encouraged by their peers to share ways of coping with chronic pain and to live full, productive lives. Group leaders are individuals who have themselves learned to function well despite their pain. NACPAC also empowers people to make informed choices; supports education and research in the field of chronic pain; and networks with organizations of similar purpose. The Association provides education about pain related problems through a series of brochures, pamphlets, and a quarterly newsletter entitled 'NACPAC Track.' In addition, speakers, videotapes, and books are available to assist members to learn about their pain problems in layperson s language. NACPAC also provides referrals to other organizations and maintains a web site at http://www3.sympatico.ca/nacpac.
Patient Resources
241
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to chronic pain. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with chronic pain. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about chronic pain. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “chronic pain” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “chronic pain”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “chronic pain” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
242 Chronic Pain
The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “chronic pain” (or a synonym) into the search box, and click “Submit Query.”
243
APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
23
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
244 Chronic Pain
libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
24
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries
245
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
246 Chronic Pain
•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
247
•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
248 Chronic Pain
•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
249
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on chronic pain: •
Basic Guidelines for Chronic Pain Chronic pain - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002164.htm Somatoform pain disorder Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000922.htm
•
Signs & Symptoms for Chronic Pain Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm
250 Chronic Pain
•
Background Topics for Chronic Pain Analgesic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm CHRONIC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Invasive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002384.htm Pain medications Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
251
CHRONIC PAIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acclimation: Adaptation of animals or plants to new climate. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetic Acids: Acetic acid and its derivatives which may be formed by substitution reactions. Mono- and di-substituted, as well as halogenated compounds have been synthesized. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acupuncture Points: Designated locations along nerves or organ meridians for inserting acupuncture needles. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA
252 Chronic Pain
and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [NIH] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction
Dictionary 253
between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH]
254 Chronic Pain
Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminopropionitrile: 3-Aminopropanenitrile. Reagent used as an intermediate in the manufacture of beta-alanine and pantothenic acid. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU]
Dictionary 255
Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete
256 Chronic Pain
absence of oxygen. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH]
Dictionary 257
Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH]
258 Chronic Pain
Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arthralgia: Pain in the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrial: Pertaining to an atrium. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign
Dictionary 259
and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axilla: The underarm or armpit. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Axotomy: Transection or severing of an axon. This type of denervation is used often in experimental studies on neuronal physiology and neuronal death or survival, toward an understanding of nervous system disease. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU]
260 Chronic Pain
Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH]
Dictionary 261
Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH]
262 Chronic Pain
Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH]
Dictionary 263
Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Cannabis: The hemp plant Cannabis sativa. Products prepared from the dried flowering tops of the plant include marijuana, hashish, bhang, and ganja. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the
264 Chronic Pain
Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH]
Dictionary 265
Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial
266 Chronic Pain
distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chamomile: Common name for several daisy-like species native to Europe and Western Asia, now naturalized in the United States and Australia. The dried flower-heads of two species, Anthemis nobilis (Chamaemelum nobile) and Matricaria recutita, have specific use as herbs. They are administered as tea, extracts, tinctures, or ointments. Chamomile contains choline, coumarins, cyanogenic glycosides, flavonoids, salicylate derivatives, tannins, and volatile oils. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH]
Dictionary 267
Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agents: Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of acetylcholine, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of muscarinic agonists, although most modern texts discourage that usage. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (paraganglia, chromaffin) of the sympathetic nervous system. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH]
268 Chronic Pain
Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Neurotrophic Factor: A neurotrophic factor that promotes the survival of various neuronal cell types and may play an important role in the injury response in the nervous system. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzymes: Substances that are necessary for the action or enhancement of action of an enzyme. Many vitamins are coenzymes. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the
Dictionary 269
action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cognitive Therapy: A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments
270 Chronic Pain
that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Compulsion: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH]
Dictionary 271
Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Contusion: A bruise; an injury of a part without a break in the skin. [EU] Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or
272 Chronic Pain
clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] Coumarins: Synthetic or naturally occurring substances related to coumarin, the deltalactone of coumarinic acid. Coumarin itself occurs in the tonka bean. The various coumarins have a wide range of proposed actions and uses including as anticoagulants, pharmaceutical aids, indicators and reagents, photoreactive substances, and antineoplastic agents. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH]
Dictionary 273
Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (prostaglandin-endoperoxide synthase) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Debrisoquin: An adrenergic neuron-blocking drug similar in effects to guanethidine. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4hydroxylase polymorphism. [NIH]
274 Chronic Pain
Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU]
Dictionary 275
Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Dextrorotatory: Turning towards the right hand. [NIH] Dextrorphan: Dextro form of levorphanol. It acts as a noncompetitive NMDA receptor antagonist, among other effects, and has been proposed as a neuroprotective agent. It is also a metabolite of dextromethorphan. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diagnostic Services: Organized services for the purpose of providing diagnosis to promote and maintain health. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dicyclomine: A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH]
276 Chronic Pain
Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disabled Children: Children with mental or physical disabilities that interfere with usual activities of daily living and that may require accommodation or intervention. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]
Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments,
Dictionary 277
pharmaceutical solutions, powders, tablets, etc. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]
Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspareunia: Painful sexual intercourse. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from
278 Chronic Pain
arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus).
Dictionary 279
[NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Enhancers: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epidural Space: Space between the dura mater and the walls of the vertebral canal. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromelalgia: Disease marked by paroxysmal, bilateral vasodilatation, particularly of the extremities, with burning pain, and increased skin temperature and redness. [NIH] Escalation: Progressive use of more harmful drugs. [NIH]
280 Chronic Pain
Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnobotany: The plant lore and agricultural customs of a people. In the field of medicine, the emphasis is on traditional medicine and the existence and medicinal uses of plants and their constituents, both historically and in modern times. [NIH] Etorphine: A narcotic analgesic morphinan used as a sedative in veterinary practice. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors. [NIH] Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Therapy: Motion of the body or its parts to relieve symptoms or to improve function, leading to physical fitness, but not physical education and training. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance
Dictionary 281
(maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]
Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH]
282 Chronic Pain
Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] Flexor: Muscles which flex a joint. [NIH] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]
Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. [NIH]
Dictionary 283
Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Galanin: A neurotransmitter. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gangliosides: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as
284 Chronic Pain
a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to
Dictionary 285
ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]
Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological
286 Chronic Pain
therapy. [NIH] Guanethidine: An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematemesis: The vomiting of blood. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH]
Dictionary 287
Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematologist: A doctor who specializes in treating diseases of the blood. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic stroke: A disorder involving bleeding within ischemic brain tissue. Hemorrhagic stroke occurs when blood vessels that are damaged or dead from lack of blood supply (infarcted), located within an area of infarcted brain tissue, rupture and transform an "ischemic" stroke into a hemorrhagic stroke. Ischemia is inadequate tissue oxygenation caused by reduced blood flow; infarction is tissue death resulting from ischemia. Bleeding irritates the brain tissues, causing swelling (cerebral edema). Blood collects into a mass (hematoma). Both swelling and hematoma will compress and displace brain tissue. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]
Herniorrhaphy: An operation to repair a hernia. [NIH] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes
288 Chronic Pain
simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocodone: Narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH]
Dictionary 289
Hydromorphone: An opioid analgesic made from morphine and used mainly as an analgesic. It has a shorter duration of action than morphine. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercalciuria: Abnormally large amounts of calcium in the urine. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertonia: Or hypertony n, pl. hypertonias or hypertonies : hypertonicity. n. Pathology: increased rigidity, tension and spasticity of the muscles. [EU] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate
290 Chronic Pain
perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH]
Dictionary 291
In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inguinal Hernia: A small part of the large or small intestine or bladder that pushes into the groin. May cause pain and feelings of pressure or burning in the groin. Often requires surgery. [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU]
292 Chronic Pain
Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH]
Dictionary 293
Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH]
294 Chronic Pain
Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Isozymes: The multiple forms of a single enzyme. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kainate: Glutamate receptor. [NIH] Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactation: The period of the secretion of milk. [EU] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH]
Dictionary 295
Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lathyrism: A paralytic condition of the legs caused by ingestion of lathyrogens, especially beta-aminopropionitrile, found in the seeds of plants of the genus Lathyrus. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU]
296 Chronic Pain
Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes
Dictionary 297
luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbosacral Plexus: The lumbar and sacral plexuses taken together. The fibers of the lumbosacral plexus originate in the lumbar and upper sacral spinal cord (L1 to S3) and innervate the lower extremities. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphedema: Edema due to obstruction of lymph vessels or disorders of the lymph nodes. [NIH]
Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malingering: Simulation of symptoms of illness or injury with intent to deceive in order to obtain a goal, e.g., a claim of physical illness to avoid jury duty. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mandibular Nerve: A branch of the trigeminal (5th cranial) nerve. The mandibular nerve carries motor fibers to the muscles of mastication and sensory fibers to the teeth and gingivae, the face in the region of the mandible, and parts of the dura. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical
298 Chronic Pain
hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH]
Dictionary 299
Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms
300 Chronic Pain
include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micturition: The passage of urine; urination. [EU] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Mitral Valve Prolapse: Abnormal protrusion of one or both of the leaflets of the mitral valve into the left atrium during systole. This may be accompanied by mitral regurgitation, systolic murmur, nonejection click, or cardiac arrhythmia. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus
Dictionary 301
surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Motor Neurons: Neurons which activate muscle cells. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spasticity: Strongly marked hypertonicity of muscles. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal Diseases: Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelin Sheath: The lipid-rich sheath investing many axons in both the central and
302 Chronic Pain
peripheral nervous systems. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (Schwann cells in the peripheral and oligodendroglia in the central nervous system). Deterioration of the sheath in demyelinating diseases is a serious clinical problem. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Nafarelin: 6-(3-(2-Naphthalenyl)-D-alanine)luteinizing hormone-releasing factor (pig). A gonadorelin analog agonist. It has been used in the treatment of central precocious puberty and endometriosis. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Neck Pain: Discomfort or more intense forms of pain that are localized to the cervical region. This term generally refers to pain in the posterior or lateral regions of the neck. [NIH]
Dictionary 303
Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. [NIH] Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]
Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with
304 Chronic Pain
atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Diseases: A general term encompassing lower motor neuron disease; peripheral nervous system diseases; and certain muscular diseases. Manifestations include muscle weakness; fasciculation; muscle atrophy; spasm; myokymia; muscle hypertonia, myalgias, and musclehypotonia. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurosurgeon: A doctor who specializes in surgery on the brain, spine, and other parts of the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH]
Dictionary 305
Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]
Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neurotrophins: A nerve growth factor. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Nonmalignant: Not cancerous. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in
306 Chronic Pain
the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norethindrone: A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [NIH] Normal Distribution: Continuous frequency distribution of infinite range. Its properties are as follows: 1) continuous, symmetrical distribution with both tails extending to infinity; 2) arithmetic mean, mode, and median identical; and 3) shape completely determined by the mean and standard deviation. [NIH] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Noscapine: A naturally occurring opium alkaloid that is a centrally acting antitussive agent. [NIH]
Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occupational Therapy: The field concerned with utilizing craft or work activities in the rehabilitation of patients. Occupational therapy can also refer to the activities themselves. [NIH]
Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligodendroglia: A class of neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal satellite cells according to their location. The most important recognized function of these cells is the formation of the insulating myelin sheaths of axons in the central nervous system. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial
Dictionary 307
operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent,
308 Chronic Pain
albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an excessive dose. [EU] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [EU]
Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies. [NIH] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]
Pain, Postoperative: Pain during the period after surgery. [NIH] Painful bladder syndrome: Another name for interstitial cystitis. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH]
Dictionary 309
Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Paraganglia, Chromaffin: Small bodies containing chromaffin cells occurring outside of the adrenal medulla, most commonly near the sympathetic ganglia and in organs such as the kidney, liver, heart and gonads. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraplegia: Severe or complete loss of motor function in the lower extremities and lower portions of the trunk. This condition is most often associated with spinal cord diseases, although brain diseases; peripheral nervous system diseases; neuromuscular diseases; and muscular diseases may also cause bilateral leg weakness. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU]
310 Chronic Pain
Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pensions: Fixed sums paid regularly to individuals. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal
Dictionary 311
(or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [NIH]
312 Chronic Pain
Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH]
Dictionary 313
Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activating Factor: A phospholipid derivative formed by platelets, basophils, neutrophils, monocytes, and macrophages. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including hypotension, thrombocytopenia, neutropenia, and bronchoconstriction. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same
314 Chronic Pain
population. [NIH] Polyneuropathies: Diseases of multiple peripheral nerves. The various forms are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH]
Dictionary 315
Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prescription drug abuse: Using two or more drugs interchangeably in an attempt to counteract the adverse effects of one with the other or to potentiate the effects of one with the other, so that an interdependent habit requiring both is formed. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It
316 Chronic Pain
incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [NIH]
Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propionic Acids: 3-carbon saturated monocarboxylic acids. [NIH] Propoxyphene: A narcotic analgesic structurally related to methadone. Only the dextroisomer has an analgesic effect; the levo-isomer appears to exert an antitussive effect. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin-Endoperoxide Synthase: An enzyme complex that catalyzes the formation of prostaglandins from the appropriate unsaturated fatty acid, molecular oxygen, and a reduced acceptor. EC 1.14.99.1. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes
Dictionary 317
a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychological Techniques: Methods used in the diagnosis and treatment of behavioral, personality, and mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH]
318 Chronic Pain
Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Pyridostigmine Bromide: A cholinesterase inhibitor with a slightly longer duration of action than neostigmine. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants. [NIH] Quadriplegia: Severe or complete loss of motor function in all four limbs which may result from brain diseases; spinal cord diseases; peripheral nervous system diseases; neuromuscular diseases; or rarely muscular diseases. The locked-in syndrome is characterized by quadriplegia in combination with cranial muscle paralysis. Consciousness is spared and the only retained voluntary motor activity may be limited eye movements. This condition is usually caused by a lesion in the upper brain stem which injures the descending cortico-spinal and cortico-bulbar tracts. [NIH]
Dictionary 319
Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radicular: Having the character of or relating to a radicle or root. [NIH] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [NIH]
Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays,
320 Chronic Pain
gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH]
Dictionary 321
Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Relaxation Techniques: The use of muscular relaxation techniques in treatment. [NIH] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which
322 Chronic Pain
restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH]
Dictionary 323
Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sciatica: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of sciatic neuropathy; radiculopathy (involving the L4, L5, S1 or S2 spinal nerve roots; often associated with intervertebral disk displacement); or lesions of the cauda equina. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seasonal Affective Disorder: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (phototherapy), during the season of recurrence. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol
324 Chronic Pain
triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensory Thresholds: The minimum amount of stimulus energy necessary to elicit a sensory response. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotonin Agonists: Agents that have an affinity for serotonin receptors and are able to mimic the effects of serotonin by stimulating the physiologic activity at the cell receptors. These compounds are used as antidepressants, anxiolytics, and in the treatment of migraine. [NIH]
Dictionary 325
Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonin agonists. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Shoulder Pain: Unilateral or bilateral pain of the shoulder. It is often caused by physical activities such as work or sports participation, but may also be pathologic in origin. [NIH] Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by
326 Chronic Pain
repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Sparteine: An alkaloid isolated from lupin beans, Lupinus luteus and Lupinus niger. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest because of genetic variation in its metabolism. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in
Dictionary 327
spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., wounds, gunshot; whiplash injuries; etc.). [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splint: A rigid appliance used for the immobilization of a part or for the correction of deformity. [NIH] Spondylitis: Inflammation of the vertebrae. [EU]
328 Chronic Pain
Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [NIH] Stellate Ganglion: A paravertebral sympathetic ganglion formed by the fusion of the inferior cervical and first thoracic ganglia. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of
Dictionary 329
nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [NIH] Stump: The end of the limb after amputation. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subliminal: Below the threshold of sensation, as a subliminal stimulus. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Sufentanil: An opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent. [NIH] Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympatholytics: Drugs that inhibit the actions of the sympathetic nervous system by any mechanism. The most common of these are the adrenergic antagonists and drugs that deplete norepinephrine or reduce the release of transmitters from adrenergic postganglionic terminals. Drugs that act in the central nervous system to reduce sympathetic activity (e.g., centrally acting alpha-2 adrenergic agonists) are included here. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects
330 Chronic Pain
similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systole: Period of contraction of the heart, especially of the ventricles. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] T cell: One type of white blood cell that attacks virus-infected cells, foreign cells, and cancer cells. T cells also produce a number of substances that regulate the immune response. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late
Dictionary 331
in appearing. [EU] Telecommunications: Transmission of information over distances via electronic means. [NIH]
Telemedicine: Delivery of health services via remote telecommunications. This includes interactive consultative and diagnostic services. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendonitis: Inflammation of tendons attached to the biceps muscle, i. e. the main flexor muscle of the upper arm. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetracaine: A potent local anesthetic of the ester type used for surface and spinal anesthesia. [NIH]
Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are antithryoid agents and/or free radical scavengers. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH]
332 Chronic Pain
Thoracic: Having to do with the chest. [NIH] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]
Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH]
Dictionary 333
Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Traction: The act of pulling. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Transcutaneous: Transdermal. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH]
334 Chronic Pain
Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigeminal Ganglion: The semilunar-shaped ganglion containing the cells of origin of most of the sensory fibers of the trigeminal nerve. It is situated within the dural cleft on the cerebral surface of the petrous portion of the temporal bone and gives off the ophthalmic, maxillary, and part of the mandibular nerves. [NIH] Trigeminal Nerve: The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. [NIH] Trigeminal Nuclei: Nuclei of the trigeminal nerve situated in the brain stem. They include the nucleus of the spinal trigeminal tract (spinal trigeminal nucleus), the principal sensory nucleus, the mesencephalic nucleus, and the motor nucleus. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines
Dictionary 335
and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urothelium: The epithelial lining of the urinary tract. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in
336 Chronic Pain
nature or in recombinant DNA technology. [NIH] Veins: The vessels carrying blood toward the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH]
Dictionary 337
Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Vomica: The profuse and sudden expectoration of pus and putrescent matter. An abnormal cavity in an organ especially in the lung, caused by suppuration and the breaking down of tissue. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wounds, Gunshot: Disruption of structural continuity of the body as a result of the discharge of firearms. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Ziconotide: A drug used in the treatment of chronic pain. Also called SNX 111. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
339
INDEX A Abdomen, 251, 261, 266, 279, 285, 292, 294, 296, 309, 327, 328, 332, 337 Abdominal, 7, 35, 53, 64, 65, 79, 97, 161, 251, 293, 309, 315 Abdominal Pain, 35, 64, 65, 97, 161, 251, 293 Aberrant, 68, 185, 194, 198, 251, 269 Ablation, 4, 101, 251 Acceptor, 251, 296, 308, 316 Acclimation, 22, 251 Accommodation, 251, 276 Acetaminophen, 11, 23, 151, 152, 168, 251 Acetic Acids, 221, 251 Acetylcholine, 43, 180, 190, 194, 251, 267, 305 Acoustic, 251, 258, 336 Activities of Daily Living, 155, 251, 276 Acupuncture Points, 23, 24, 251 Adaptability, 135, 251, 265 Adaptation, 27, 49, 64, 72, 80, 133, 138, 251, 313 Adenine, 169, 251, 252 Adenosine, 36, 52, 168, 169, 182, 194, 251, 252, 263, 312 Adenosine Triphosphate, 168, 169, 182, 252, 312 Adenovirus, 21, 161, 252 Adenylate Cyclase, 42, 252 Adhesions, 65, 252 Adjustment, 56, 64, 85, 103, 134, 137, 138, 251, 252 Adjuvant, 4, 13, 16, 46, 51, 63, 95, 164, 198, 221, 252, 284 Adolescence, 64, 252 Adrenal Cortex, 252, 272, 315 Adrenal Medulla, 45, 184, 252, 264, 267, 279, 305, 309 Adrenergic, 36, 51, 61, 160, 177, 184, 194, 252, 254, 256, 257, 273, 276, 279, 286, 316, 319, 329, 335 Adrenergic Agonists, 36, 51, 61, 252, 329 Adrenergic Antagonists, 252, 329 Adrenergic beta-Antagonists, 252, 256 Adverse Effect, 47, 151, 182, 198, 252, 315, 325 Aerobic, 28, 252, 280 Aerobic Exercise, 28, 252
Afferent, 7, 8, 38, 39, 40, 43, 52, 61, 173, 252, 272, 312, 315, 327 Affinity, 47, 60, 148, 181, 184, 252, 253, 258, 275, 324, 326 Age Groups, 68, 253 Aged, 80 and Over, 253 Aggravation, 8, 253 Agoraphobia, 253, 309, 311 Akathisia, 253, 257 Alanine, 253, 254, 302 Alertness, 253, 263 Algorithms, 253, 261 Alimentary, 253, 294 Alkaline, 253, 254, 263, 311 Alkaloid, 253, 260, 262, 263, 268, 301, 305, 306, 309, 312, 319, 326, 328 Allergen, 253, 274, 324 Allogeneic, 10, 253, 285 Alpha-1, 253, 254 Alternative medicine, 28, 117, 219, 253 Ameliorated, 43, 253 Ameliorating, 165, 193, 195, 196, 253 Amenorrhea, 253, 306 Amine, 254, 288 Amino Acid Sequence, 193, 254, 256, 260, 284, 316 Amino Acids, 130, 181, 193, 194, 254, 260, 280, 284, 304, 310, 314, 317, 322, 333 Aminopropionitrile, 254, 295 Amitriptyline, 141, 142, 254 Ammonia, 254, 285 Amphetamine, 254, 260, 275 Amplification, 26, 254 Ampulla, 254, 279 Amputation, 141, 198, 254, 329 Amygdala, 254, 259, 296, 331 Anaesthesia, 254, 291 Anal, 17, 49, 111, 254, 282, 296 Analeptic, 254, 328 Analog, 4, 26, 55, 60, 65, 254, 275, 294, 295, 302 Analogous, 154, 254, 333 Anaphylactic, 164, 255, 313 Anaphylatoxins, 255, 270 Anaphylaxis, 255 Anaplasia, 255, 303 Anatomical, 15, 54, 255, 258, 261, 290, 323 Androgenic, 255, 306
340 Chronic Pain
Androgens, 252, 255, 272 Anemia, 47, 255, 287 Anesthesia, 12, 29, 37, 53, 71, 80, 88, 103, 120, 121, 148, 150, 154, 165, 167, 169, 171, 177, 195, 197, 255, 272, 278, 294, 315, 329, 331 Anesthetics, 13, 38, 60, 167, 169, 171, 172, 175, 192, 221, 255, 259, 279 Angina, 252, 255, 316 Angina Pectoris, 252, 255, 316 Angiogenesis, 255, 298 Angiotensin-Converting Enzyme Inhibitors, 255, 256 Animal model, 6, 9, 13, 21, 29, 35, 45, 51, 63, 163, 180, 190, 218, 255 Anions, 255, 293 Anoxia, 146, 147, 150, 166, 170, 196, 197, 255 Antagonism, 46, 61, 146, 191, 194, 256, 263 Anterior Cerebral Artery, 256, 266 Antiallergic, 256, 272 Antibacterial, 256, 327 Antibiotic, 256, 310, 327 Antibodies, 60, 199, 256, 257, 286, 288, 290, 297, 313, 319 Antibody, 68, 166, 180, 253, 256, 269, 286, 288, 290, 291, 298, 319, 320, 324, 327 Anticholinergic, 254, 256 Anticoagulant, 256, 317 Anticonvulsant, 149, 256, 264 Antidepressant, 138, 198, 254, 256, 262 Antiemetic, 256, 257 Antiepileptic, 149, 256 Antigen, 166, 253, 255, 256, 257, 269, 288, 289, 290, 291, 298, 324 Antigen-Antibody Complex, 256, 269 Antihypertensive, 170, 256, 286 Antihypertensive Agents, 170, 256 Anti-inflammatory, 4, 5, 11, 12, 57, 163, 168, 187, 189, 198, 251, 256, 258, 272, 284, 291, 323 Anti-Inflammatory Agents, 12, 163, 257, 258, 272 Antineoplastic, 257, 272, 289 Antioxidants, 163, 257 Antipsychotic, 170, 209, 257, 304 Antipyretic, 11, 251, 257, 319 Antiserum, 62, 257 Antispasmodic, 257, 275, 307 Antitussive, 257, 275, 306, 307, 316 Antiviral, 10, 257 Anus, 254, 257, 261, 320
Anxiety Disorders, 178, 193, 257, 309 Anxiolytic, 168, 257 Apnea, 176, 257 Aponeurosis, 257, 283 Applicability, 72, 169, 257 Aqueous, 257, 259, 273, 278, 288 Arachidonic Acid, 163, 257, 273, 278, 295, 316 Arginine, 63, 255, 258, 305 Aromatic, 46, 258, 260, 311 Arrhythmia, 187, 188, 258, 300, 326 Arterial, 164, 258, 262, 265, 284, 289, 293, 317, 330, 333 Arteries, 258, 261, 266, 271, 294, 299, 302, 332 Arterioles, 258, 261 Arteriovenous, 258, 266 Arthralgia, 189, 258 Articular, 258, 307 Aspartate, 79, 105, 146, 147, 148, 150, 165, 169, 170, 191, 196, 197, 258, 275, 294 Asphyxia, 146, 147, 150, 170, 197, 258 Aspirin, 151, 152, 168, 179, 187, 258 Assay, 13, 51, 53, 190, 258 Astrocytes, 258, 300 Asymptomatic, 40, 258 Atrial, 181, 258 Atrium, 258, 300, 336 Atrophy, 166, 196, 258, 304 Attenuation, 163, 258 Atypical, 258, 306 Auditory, 212, 258, 315 Auditory nerve, 212, 258 Autacoids, 258, 291 Autoimmune disease, 161, 258, 259, 301 Autoimmunity, 198, 199, 259 Autonomic, 50, 251, 257, 259, 272, 283, 284, 303, 305, 310, 314, 326, 327, 329 Autonomic Nervous System, 51, 259, 303, 310, 326, 329 Autoradiography, 36, 259 Axilla, 259, 262 Axonal, 192, 259, 314 Axons, 59, 166, 259, 301, 303, 306, 307, 310, 315, 327 Axotomy, 59, 259 B Back Pain, 15, 16, 17, 19, 22, 49, 64, 155, 167, 240, 259 Bacteria, 256, 259, 279, 281, 282, 296, 299, 300, 327, 333, 335 Bacterial Physiology, 251, 259
Index 341
Bactericidal, 259, 280 Bacteriophage, 259, 333 Barbiturate, 259, 271 Basal Ganglia, 257, 259, 262, 267, 283, 296 Basal Ganglia Diseases, 259, 267 Base, 33, 48, 251, 259, 274, 284, 294, 311, 331 Basement Membrane, 260, 281 Basophils, 260, 285, 295, 313 Behavioral Symptoms, 48, 260 Benign, 260, 283, 286, 303, 319 Benzene, 260 Benzodiazepines, 190, 221, 260 Berberine, 175, 260 Beta-Endorphin, 161, 260 Bewilderment, 260, 270 Bilateral, 26, 78, 260, 279, 309, 322, 325 Bile, 260, 283, 296, 328 Binding Sites, 175, 181, 260 Biochemical, 6, 14, 30, 31, 43, 45, 47, 193, 260, 295, 307, 311, 324 Biogenic Amines, 193, 260 Biological therapy, 260, 286 Biomarkers, 40, 260 Biopsy, 39, 41, 65, 261, 310 Biopsy specimen, 41, 261 Biosynthesis, 56, 257, 261, 311 Biotechnology, 69, 70, 115, 210, 219, 231, 261 Bipolar Disorder, 149, 178, 261 Bladder, 7, 25, 40, 42, 152, 189, 261, 273, 283, 291, 301, 304, 316, 335, 337 Blastocyst, 261, 270, 312 Bloating, 261, 293 Blood Cell Count, 261, 287 Blood Coagulation, 261, 263, 332 Blood Glucose, 261, 287, 292 Blood Platelets, 261, 324, 332 Blood pressure, 49, 53, 59, 169, 177, 256, 261, 264, 266, 283, 284, 289, 300, 325, 326 Body Fluids, 260, 261, 277, 326, 334 Body Regions, 60, 261 Bone Marrow, 260, 261, 290, 297, 300, 328 Bone metastases, 4, 261 Bowel, 36, 254, 261, 275, 291, 292, 328 Bowel Movement, 261, 275, 328 Brachial, 103, 166, 262, 298 Brachial Plexus, 103, 262, 298 Bradycardia, 169, 262 Bradykinin, 262, 305 Brain Diseases, 262, 309, 318 Brain Ischemia, 262, 266
Brain Stem, 262, 265, 266, 271, 318, 334 Branch, 214, 247, 262, 278, 297, 309, 318, 327, 330, 331, 332 Breakdown, 262, 275, 283, 307 Bronchi, 262, 279, 294 Bronchial, 164, 262, 288 Bronchitis, 262, 267 Bronchoconstriction, 262, 313 Bronchodilator, 262, 294 Bulbar, 262, 318 Bupivacaine, 172, 262, 295 Buprenorphine, 73, 174, 262 Bupropion, 160, 183, 262 Burns, 55, 67, 70, 79, 80, 85, 98, 103, 187, 262 Burns, Electric, 262 C Caffeine, 190, 221, 254, 263 Calcineurin, 61, 263 Calcium, 4, 21, 38, 60, 163, 180, 185, 187, 188, 190, 191, 218, 256, 263, 269, 289, 298, 308, 309, 317, 325 Calcium channel blocker, 4, 218, 256, 263 Calcium Channel Blockers, 4, 256, 263 Calcium Channels, 263, 309 Calcium Oxalate, 263, 308 Calmodulin, 263 Cannabidiol, 263 Cannabinoids, 41, 115, 162, 163, 263 Cannabinol, 263 Cannabis, 44, 114, 119, 163, 218, 263, 331 Capsaicin, 8, 13, 51, 61, 180, 183, 190, 199, 221, 263 Capsules, 264, 276, 284 Carbamazepine, 67, 172, 264 Carbohydrate, 264, 272, 284, 314, 323 Carcinogen, 264, 331 Carcinogenic, 260, 264, 292, 315, 328 Cardiac arrest, 146, 147, 150, 156, 163, 166, 170, 191, 196, 197, 264 Cardiorespiratory, 252, 264 Cardioselective, 264, 316 Cardiovascular, 49, 169, 173, 177, 254, 263, 264, 275, 280, 295, 324, 326, 332 Cardiovascular disease, 173, 264 Carotene, 264, 322 Carpal Tunnel Syndrome, 198, 264 Case report, 85, 86, 264, 268 Case series, 24, 109, 114, 119, 264, 268 Catecholamine, 264, 276, 311 Catheters, 221, 264 Cathode, 264, 278
342 Chronic Pain
Cations, 180, 264, 293 Cauda Equina, 265, 323 Caudal, 265, 275, 289, 314 Causal, 6, 34, 56, 57, 150, 197, 265, 324, 331 Cell Death, 191, 265, 303 Cell Differentiation, 265, 325 Cell Division, 259, 265, 285, 298, 313, 316 Cell membrane, 165, 166, 196, 263, 265, 274, 283, 294, 302, 326, 337 Cell proliferation, 265, 325 Cell Survival, 265, 285 Cellulose, 265, 313 Central Nervous System Infections, 265, 286 Centrifugation, 265, 287 Cerebellar, 265, 334 Cerebellar Diseases, 265, 334 Cerebellum, 262, 265, 266, 272 Cerebral Infarction, 146, 147, 150, 170, 197, 265, 266 Cerebral Palsy, 67, 266, 327 Cerebrospinal, 15, 91, 266 Cerebrospinal fluid, 15, 91, 266 Cerebrovascular, 146, 147, 150, 170, 197, 259, 263, 264, 266 Cerebrovascular Disorders, 146, 147, 150, 170, 197, 266 Cerebrum, 265, 266, 272, 312 Cervical, 84, 164, 166, 262, 266, 298, 302, 328 Cervix, 266, 282 Chamomile, 4, 266 Character, 4, 255, 266, 274, 319 Chemoreceptor, 257, 266 Chemotactic Factors, 266, 270 Chemotherapy, 7, 198, 266 Chest wall, 266, 313 Chiropractic, 118, 266 Cholecystokinin, 108, 266 Cholera, 267, 325 Cholesterol, 260, 267, 272, 328 Choline, 266, 267 Cholinergic, 51, 190, 254, 257, 267, 301, 305 Cholinergic Agents, 51, 267 Chorea, 157, 163, 257, 267 Choreatic Disorders, 267 Chorioretinitis, 267, 322 Choroid, 267, 322 Chromaffin Cells, 10, 267, 309 Chromic, 66, 267 Chromium, 267 Chromosomal, 254, 267
Chromosome, 267, 286, 296 Chronic Disease, 4, 173, 186, 267 Chronic Fatigue Syndrome, 160, 161, 183, 267 Chronic Obstructive Pulmonary Disease, 189, 267 Ciliary, 43, 268 Ciliary Neurotrophic Factor, 43, 268 Circadian, 57, 268 CIS, 268, 322 Clamp, 6, 21, 33, 268 Clinical Medicine, 268, 314 Clinical Protocols, 68, 268 Clinical study, 268, 271 Clinical trial, 5, 10, 23, 24, 64, 65, 68, 106, 124, 141, 143, 149, 231, 268, 271, 277, 310, 317, 320 Clonic, 268, 271 Cloning, 261, 268 Coca, 268 Cocaine, 44, 176, 268 Cochlea, 212, 268 Cochlear, 268, 332, 336 Cochlear Diseases, 268, 332 Cod Liver Oil, 268, 278 Codeine, 36, 151, 168, 268, 275, 288, 307, 308 Coenzymes, 268, 305 Cofactor, 182, 268, 317, 332 Cognition, 34, 78, 81, 150, 165, 195, 197, 269, 304 Cognitive restructuring, 34, 56, 269, 328 Cognitive Therapy, 4, 205, 269 Colitis, 164, 269, 291, 293 Collagen, 11, 181, 260, 269, 271, 281, 282, 283, 292, 298, 313, 315 Collapse, 239, 255, 262, 269, 313, 326 Combinatorial, 37, 269 Comorbidity, 21, 73, 269 Complement, 37, 55, 114, 255, 269, 270, 284, 324 Complementary and alternative medicine, 32, 42, 117, 118, 131, 270 Complementary medicine, 118, 270 Compress, 270, 287 Compulsion, 270, 337 Computational Biology, 231, 270 Computed tomography, 120, 270 Computerized axial tomography, 270 Computerized tomography, 270 Conception, 54, 270, 271, 328 Conduction, 154, 270, 302, 331
Index 343
Cone, 9, 270, 329 Confusion, 161, 187, 270, 276, 289, 304 Congestion, 177, 257, 270 Congestive heart failure, 177, 270 Conjugated, 270, 273 Conjunctiva, 270, 334 Connective Tissue, 109, 181, 261, 269, 271, 282, 283, 284, 297, 301, 310, 322, 330 Connective Tissue Cells, 271 Connective Tissue Diseases, 109, 271 Consciousness, 254, 271, 274, 276, 287, 318, 328 Constipation, 161, 187, 191, 257, 271, 293, 325 Constitutional, 271, 301, 322 Constriction, 41, 271, 294, 335 Continuous infusion, 168, 271 Contraception, 271, 306 Contraindications, ii, 271 Control group, 20, 23, 49, 66, 271, 320 Controlled clinical trial, 28, 42, 271, 320 Contusion, 30, 59, 271 Convulsants, 190, 271 Convulsive, 150, 197, 271, 278 Coordination, 17, 34, 65, 173, 265, 271, 301 Cornea, 271, 337 Coronary, 157, 255, 264, 271, 272, 299, 302 Coronary heart disease, 264, 271 Coronary Thrombosis, 272, 299, 302 Corpus, 181, 272, 310, 312, 315, 331 Corpus Luteum, 181, 272, 315 Cortex, 166, 262, 272, 280, 282, 315 Cortical, 19, 125, 157, 272, 280, 315, 324 Cortices, 26, 272 Corticosteroid, 220, 272 Cortisol, 12, 59, 272 Cost Savings, 28, 272 Coumarins, 266, 272 Cranial, 125, 174, 258, 265, 272, 284, 286, 293, 297, 303, 307, 310, 318, 334, 336 Cranial Nerves, 174, 272, 303 Craniocerebral Trauma, 259, 272, 286, 332 Critical Care, 92, 272 Curare, 272, 301 Curative, 272, 305, 331 Cutaneous, 26, 33, 67, 155, 272, 297, 309 Cyanide, 166, 196, 273 Cyclic, 45, 252, 263, 273, 286, 305, 311, 312, 316, 323 Cyclooxygenase Inhibitors, 5, 273 Cysteine, 194, 273 Cystine, 273
Cystitis, 7, 40, 42, 63, 152, 166, 196, 273, 308 Cytochrome, 151, 273 Cytokine, 6, 12, 22, 40, 56, 273 Cytomegalovirus, 194, 273 Cytoplasm, 260, 265, 273, 285, 301, 305, 322, 330 Cytotoxic, 263, 273, 319, 320, 325 D Data Collection, 7, 34, 273 Databases, Bibliographic, 231, 273 Debrisoquin, 151, 273 Decarboxylation, 260, 274, 288 Defense Mechanisms, 164, 274 Degenerative, 124, 146, 147, 150, 157, 163, 165, 167, 170, 187, 188, 196, 197, 274, 301, 307 Delirium, 168, 257, 274 Delivery of Health Care, 274, 286 Delusions, 274, 318 Dementia, 48, 146, 156, 157, 166, 186, 196, 257, 274 Demyelinating Diseases, 274, 302 Dendrites, 274, 303, 304 Dendritic, 274, 327 Density, 39, 40, 265, 274, 306, 326 Dentists, 58, 274 Depersonalization, 274, 309, 323 Depolarization, 33, 53, 274, 325 Derealization, 274, 309 Desensitization, 36, 199, 274 Deuterium, 275, 288 Dextroamphetamine, 221, 254, 275 Dextromethorphan, 73, 78, 143, 151, 275 Dextrorotatory, 160, 184, 275 Dextrorphan, 151, 275 Diabetes Mellitus, 39, 275, 285, 287 Diabetic Retinopathy, 150, 275 Diagnostic procedure, 145, 219, 275 Diagnostic Services, 275, 331 Diarrhea, 182, 275, 293 Diastolic, 275, 289 Dicyclomine, 275 Diencephalon, 266, 275, 289, 315, 331 Digestion, 53, 253, 260, 261, 275, 292, 296, 328 Digestive system, 144, 275 Dihydropyridines, 170, 171, 275 Dilatation, 275, 315, 335 Dilation, 181, 262, 275, 335 Dimethyl, 176, 275 Diploid, 276, 313
344 Chronic Pain
Direct, iii, 6, 8, 13, 25, 34, 41, 44, 48, 62, 68, 153, 163, 172, 187, 223, 268, 269, 276, 309, 319, 321, 330 Disabled Children, 68, 276 Disinfectant, 276, 280 Dislocation, 181, 276, 328 Disorientation, 270, 274, 276 Dissociation, 20, 252, 276, 293 Dissociative Disorders, 276 Distal, 40, 166, 259, 276, 310, 314, 315, 317 Diuresis, 263, 276 Diuretics, Thiazide, 256, 276 Dizziness, 161, 168, 276, 309 Dopamine, 159, 176, 194, 254, 257, 262, 268, 275, 276, 300, 311 Dorsal, 9, 21, 28, 31, 33, 36, 38, 41, 43, 46, 53, 59, 63, 90, 153, 174, 276, 314, 327 Dorsum, 276, 283 Dosage Forms, 176, 276 Double-blinded, 6, 277 Drive, ii, vi, 6, 43, 113, 159, 199, 202, 277 Drug Interactions, 118, 224, 277 Drug Tolerance, 277, 333 Duct, 254, 277, 281, 323 Duodenal Ulcer, 189, 277 Duodenum, 260, 277, 279, 328 Dura mater, 277, 279 Dynorphins, 277, 307 Dyskinesia, 257, 277 Dyspareunia, 68, 277 Dysphoric, 178, 277 Dyspnea, 277, 309 Dystonia, 153, 257, 277 Dystrophy, 19, 157, 160, 183, 236, 277 E Eating Disorders, 176, 277 Eclampsia, 182, 277 Ectopic, 192, 277 Edema, 275, 277, 287, 293, 297 Effector, 194, 251, 269, 277, 304, 305, 311 Effector cell, 277, 304, 305 Efficacy, 6, 7, 11, 12, 13, 17, 19, 20, 21, 23, 24, 28, 34, 37, 42, 46, 47, 51, 56, 62, 65, 67, 68, 71, 73, 81, 84, 87, 95, 101, 137, 142, 169, 178, 189, 277, 296, 334 Eicosanoids, 273, 277 Ejaculation, 178, 278, 324 Elastin, 269, 271, 278, 281 Elective, 278 Electroacupuncture, 28, 278 Electroconvulsive Therapy, 120, 278 Electrolysis, 255, 264, 278
Electrolyte, 272, 274, 278, 300, 314, 326 Electrons, 259, 264, 278, 293, 308, 319, 320 Electrophysiological, 21, 31, 38, 41, 54, 278 Electroshock, 149, 278 Embryo, 261, 265, 278, 291 Emesis, 163, 191, 278 Emphysema, 267, 278 Empirical, 20, 55, 56, 278 Emulsion, 164, 259, 278, 282 Endemic, 210, 267, 278, 328 Endocrine System, 278, 304 Endometrial, 278, 279 Endometriosis, 24, 65, 181, 238, 279, 302, 306 Endometrium, 278, 279, 299 Endorphin, 161, 260, 279 Endoscope, 279 Endoscopic, 87, 279 Endothelium, 279, 305 Endothelium-derived, 279, 305 Endotoxin, 279, 335 Energetic, 95, 123, 279 Enhancers, 165, 195, 279 Enkephalin, 29, 260, 279, 316 Environmental Health, 230, 232, 279 Enzymatic, 182, 260, 263, 264, 269, 279, 288, 322 Epidemic, 210, 279, 328 Epidural, 53, 152, 153, 161, 279 Epidural Space, 161, 279 Epigastric, 279, 309 Epinephrine, 184, 252, 260, 267, 276, 279, 294, 305, 335 Epithelial, 279, 335 Epithelium, 260, 279, 337 Erythrocytes, 255, 261, 279, 321, 324 Erythromelalgia, 182, 279 Escalation, 16, 279 Esophagus, 275, 280, 328, 332 Essential Tremor, 157, 280 Estrogen, 31, 58, 280 Ethanol, 38, 280 Ethnobotany, 176, 280 Etorphine, 46, 280 Eukaryotic Cells, 280, 290 Evacuation, 271, 280, 308 Evoke, 61, 280, 328 Excitability, 6, 21, 41, 52, 280, 302, 303, 319 Excitation, 14, 52, 146, 147, 150, 170, 191, 197, 199, 266, 280 Excitatory Amino Acid Agonists, 280, 294
Index 345
Excitatory Amino Acid Antagonists, 163, 280 Excitatory Amino Acids, 31, 61, 146, 147, 148, 150, 165, 170, 186, 195, 196, 197, 280, 304 Excitotoxicity, 150, 165, 186, 196, 197, 280 Exercise Test, 280, 281 Exercise Therapy, 23, 280 Exercise Tolerance, 34, 280 Exhaustion, 164, 256, 281 Exocrine, 266, 281, 309 Exogenous, 10, 281 Extracellular, 30, 33, 169, 181, 185, 188, 194, 199, 258, 271, 281, 282, 298, 299, 326 Extracellular Matrix, 181, 271, 281, 282, 298 Extracellular Matrix Proteins, 281, 298 Extracellular Space, 281, 299 Extraction, 176, 178, 281 Extrapyramidal, 253, 257, 276, 281 Extremity, 262, 281, 298, 323 Exudate, 267, 281, 307 Eye Infections, 252, 281 Eye Movements, 281, 318 F Facial, 12, 281, 326 Facial Pain, 12, 281 Family Planning, 231, 281 Fat, 257, 261, 264, 272, 281, 284, 296, 301, 322 Fatigue, 22, 34, 42, 58, 160, 161, 175, 202, 238, 267, 281, 287 Fatty acids, 277, 281, 316, 332 Febrile, 149, 282 Feces, 271, 282, 328 Fentanyl, 152, 174, 218, 219, 221, 224, 282 Fibrin, 261, 282, 332 Fibrinogen, 282, 332 Fibroblasts, 271, 282, 292 Fibrosis, 282, 323 Fissure, 282, 315 Fixation, 282, 324 Flexion, 220, 282 Flexor, 282, 331 Follicular Phase, 58, 282 Follow-Up Studies, 22, 282 Forearm, 261, 282, 298 Fractionation, 60, 178, 282 Free Radical Scavengers, 163, 282, 331 Frontal Lobe, 256, 265, 283, 315 Fructose, 283, 288
Functional magnetic resonance imaging, 19, 283 Fundus, 282, 283, 307 G Galanin, 56, 283 Gallbladder, 251, 266, 275, 283 Gamma Rays, 283, 319, 320 Ganglia, 9, 52, 63, 153, 166, 173, 251, 259, 283, 303, 309, 310, 327, 328, 329 Ganglion, 21, 28, 38, 41, 46, 90, 283, 307, 328, 334, 336, 337 Ganglionic Blockers, 256, 283 Gangliosides, 163, 283 Gangrenous, 283, 325 Gap Junctions, 283, 330 Gas, 254, 283, 288, 293, 305, 313, 335, 336 Gastric, 187, 276, 283, 288 Gastrin, 283, 288 Gastrointestinal, 40, 178, 179, 188, 191, 262, 266, 275, 279, 280, 283, 295, 324, 326, 329, 334 Gastrointestinal tract, 280, 283, 295, 324, 334 Gelatin, 283, 285, 329 Gels, 154, 284 Gemcitabine, 7, 284 Gene Expression, 21, 31, 59, 186, 199, 284 Generator, 21, 284 Genetic Code, 284, 306 Genetic Engineering, 161, 261, 268, 284 Genetics, 29, 284 Genital, 284, 335 Genitourinary, 284, 335 Genomics, 29, 284 Germ Cells, 284, 298, 308, 326 Gestation, 284, 310, 312 Gland, 10, 252, 284, 289, 297, 298, 309, 312, 316, 324, 328, 332 Glossopharyngeal Nerve, 281, 284 Glucocorticoids, 252, 272, 284 Glucokinase, 284, 288 Glucose, 261, 265, 267, 275, 284, 285, 287, 288, 289, 292, 323, 326 Glucose Intolerance, 275, 285 Glutamate, 9, 30, 35, 61, 146, 147, 148, 150, 170, 180, 185, 191, 197, 275, 280, 285, 294, 299 Glutamic Acid, 191, 285, 315 Glutamine, 47, 285 Glycine, 148, 149, 191, 285, 328 Glycoprotein, 282, 285, 332, 334 Gonad, 285
346 Chronic Pain
Gonadal, 48, 285, 328 Gonadorelin, 285, 295, 302 Gonadotropin, 24, 285, 295 Governing Board, 285, 314 Graft, 10, 285, 288, 290 Graft Rejection, 285, 290 Granulocytes, 285, 325, 337 Gravis, 285, 303, 318 Groin, 97, 285, 291 Growth factors, 13, 43, 51, 194, 285, 303 Guanethidine, 273, 286 Guanylate Cyclase, 286, 305 H Habitat, 286, 305 Habitual, 55, 266, 286 Haematemesis, 278, 286 Half-Life, 151, 286 Haploid, 286, 313 Haptens, 253, 286 Headache Disorders, 286 Health Behavior, 94, 107, 286 Health Care Costs, 17, 286 Health Expenditures, 286 Health Services, 274, 286, 331 Health Status, 44, 50, 117, 286 Heart attack, 264, 286 Heart failure, 255, 287 Hematocrit, 47, 261, 287 Hematologist, 54, 287 Hematoma, 287 Heme, 29, 273, 287, 308 Hemoglobin, 47, 255, 261, 279, 287, 295 Hemorrhage, 272, 286, 287, 328, 337 Hemorrhagic stroke, 146, 147, 150, 170, 197, 287 Hemorrhoids, 164, 287 Hemostasis, 287, 324 Hepatic, 166, 196, 274, 287, 300 Hepatic Encephalopathy, 166, 196, 287 Hepatotoxic, 11, 287 Hepatotoxicity, 11, 287 Hereditary, 47, 267, 271, 287, 301, 303, 313 Heredity, 284, 287 Hernia, 79, 97, 287 Herniorrhaphy, 71, 287 Herpes, 10, 28, 39, 179, 198, 287, 288 Herpes Zoster, 10, 39, 179, 198, 288 Heterogeneity, 253, 288 Hexokinase, 47, 288 Histamine, 194, 255, 257, 260, 288 Histidine, 288 Homeostasis, 14, 35, 169, 188, 288, 326
Homologous, 288, 324, 330 Hormonal, 31, 51, 58, 61, 64, 181, 258, 267, 272, 288 Hormone therapy, 24, 288 Host, 45, 69, 164, 180, 198, 199, 259, 288, 290, 295, 336 Hybrid, 288 Hybridization, 51, 288 Hybridomas, 288, 292 Hydrocodone, 151, 152, 288 Hydrogen, 19, 179, 251, 254, 259, 264, 275, 281, 288, 296, 300, 306, 308, 311, 317 Hydrogen Peroxide, 288, 296 Hydrolysis, 165, 196, 288, 312, 314, 317 Hydromorphone, 71, 86, 114, 151, 152, 174, 289 Hydrophilic, 164, 194, 289 Hydrophobic, 194, 289 Hydroxylysine, 269, 289 Hydroxyproline, 269, 289 Hydroxyurea, 47, 289 Hyperalgesia, 6, 13, 19, 29, 31, 33, 35, 37, 38, 51, 60, 61, 62, 63, 179, 187, 198, 289 Hypercalcemia, 187, 188, 289 Hypercalciuria, 187, 188, 289 Hypersensitivity, 26, 36, 43, 51, 75, 253, 255, 274, 289, 295, 322, 324 Hypertension, 58, 180, 182, 252, 255, 256, 263, 264, 289, 293, 314, 316 Hyperthyroidism, 289, 316 Hypertonia, 164, 289, 304 Hypnotic, 17, 259, 289 Hypoglycaemia, 274, 289 Hypoglycemia, 146, 147, 148, 150, 165, 166, 170, 191, 195, 196, 197, 289 Hypotension, 168, 169, 180, 257, 271, 283, 289, 313 Hypotensive, 169, 289 Hypothalamic, 34, 289 Hypothalamus, 51, 259, 262, 275, 279, 285, 289, 296, 312, 315, 329, 331 Hypothermia, 154, 169, 289 Hypothyroidism, 198, 289 Hypoxia, 147, 166, 196, 262, 266, 274, 289 Hysterectomy, 53, 238, 290 I Id, 116, 126, 238, 239, 246, 248, 290 Immune function, 94, 107, 290 Immune response, 63, 166, 252, 256, 259, 272, 285, 286, 290, 324, 329, 330, 336 Immune Sera, 290
Index 347
Immune system, 6, 259, 260, 277, 290, 295, 297, 301, 302, 335, 337 Immunity, 29, 253, 290, 333 Immunization, 164, 290, 324 Immunodeficiency, 118, 150, 197, 290 Immunofluorescence, 46, 290 Immunohistochemistry, 54, 290 Immunologic, 40, 266, 290, 320 Immunology, 252, 290 Immunophilin, 263, 290 Immunosuppressive, 9, 263, 290 Immunosuppressive therapy, 9, 290 Immunotherapy, 164, 260, 274, 290 Impairment, 27, 50, 73, 138, 219, 260, 266, 274, 277, 281, 290, 299, 318 Implantation, 270, 290 Impotence, 164, 178, 290, 309 In situ, 9, 12, 43, 51, 63, 290 In Situ Hybridization, 43, 290 In vitro, 6, 11, 13, 21, 37, 38, 291, 333 In vivo, 9, 11, 13, 14, 21, 29, 37, 51, 186, 191, 291, 299, 332 Incision, 51, 291, 293 Incontinence, 146, 147, 150, 154, 165, 166, 170, 176, 180, 191, 195, 196, 197, 275, 291 Indicative, 203, 291, 309, 335 Indomethacin, 179, 291 Induction, 53, 55, 181, 255, 257, 278, 283, 291, 294 Infant, Newborn, 253, 291 Infarction, 262, 265, 287, 291 Infertility, 24, 291 Infiltration, 291, 315, 337 Inflammatory bowel disease, 189, 291 Informed Consent, 96, 291 Infusion, 62, 86, 291 Ingestion, 11, 291, 295, 313 Inguinal, 71, 74, 79, 291 Inguinal Hernia, 74, 79, 291 Inhalation, 38, 291, 313 Initiation, 10, 63, 220, 292 Inlay, 292, 321 Innervation, 262, 292, 298, 311, 323, 332 Inositol, 292, 299, 323 Inotropic, 276, 292 Inpatients, 3, 292 Insight, 30, 31, 62, 292 Insomnia, 57, 91, 127, 236, 292, 315, 325 Insulator, 292, 301, 302 Insulin, 34, 292 Insulin-dependent diabetes mellitus, 292 Insulin-like, 34, 292
Intensive Care, 164, 292 Interleukin-6, 6, 292 Intermittent, 292, 296 Interstitial, 7, 40, 42, 63, 152, 181, 281, 292, 308, 321 Interstitial Collagenase, 181, 292 Intervertebral, 292, 296, 319, 323 Intervertebral Disk Displacement, 292, 296, 319, 323 Intestinal, 187, 264, 266, 292 Intestine, 261, 292, 295 Intoxication, 274, 293, 337 Intracellular, 6, 33, 53, 159, 182, 188, 193, 199, 263, 291, 293, 298, 299, 305, 314, 316, 320, 323, 325 Intracellular Membranes, 293, 298 Intracranial Embolism, 266, 293 Intracranial Embolism and Thrombosis, 266, 293 Intracranial Hypertension, 286, 293, 332 Intraocular, 177, 184, 293 Intraocular pressure, 177, 184, 293 Intrathecal, 13, 14, 16, 36, 62, 86, 89, 91, 98, 114, 115, 125, 142, 218, 293 Intravenous, 182, 291, 293 Intrinsic, 43, 66, 253, 260, 293 Invasive, 4, 5, 68, 87, 88, 122, 157, 250, 290, 293, 297 Involuntary, 158, 259, 267, 280, 293, 302, 321, 326 Ion Channels, 8, 13, 38, 188, 258, 293, 305, 330 Ion Exchange, 265, 293 Ionization, 293 Ionizing, 293, 319 Ions, 172, 180, 185, 259, 263, 276, 278, 288, 293, 300, 317, 326 Iontophoresis, 54, 293 Irritable Bowel Syndrome, 35, 40, 48, 60, 176, 189, 203, 293 Ischemic stroke, 157, 294 Isoenzyme, 288, 294 Isoproterenol, 184, 294 Isotonic, 164, 294 Isozymes, 61, 294 J Joint, 32, 48, 50, 58, 63, 91, 214, 239, 258, 282, 294, 297, 307, 328, 330 K Kainate, 148, 294 Kainic Acid, 165, 196, 294 Kb, 230, 294
348 Chronic Pain
Ketamine, 86, 94, 294 Keto, 147, 294 Kidney stone, 294, 308 Kinetics, 9, 29, 263, 294 L Labile, 269, 294 Labyrinth, 268, 294, 336 Laceration, 294, 331 Lactation, 31, 294 Laparoscopy, 24, 294 Large Intestine, 275, 292, 295, 320, 326 Laser therapy, 71, 119, 295 Latency, 155, 295 Latent, 29, 33, 295 Lathyrism, 146, 147, 150, 170, 197, 295 Lectin, 295, 298 Lesion, 60, 84, 295, 296, 318, 324, 330, 335 Lethal, 259, 273, 295 Lethargy, 168, 289, 295 Leucine, 181, 260, 295 Leukemia, 56, 143, 295 Leukocytes, 260, 261, 266, 285, 291, 295, 300, 305, 334 Leukotrienes, 257, 278, 295 Leuprolide, 65, 295 Levo, 295, 316 Levorphanol, 152, 275, 295 Library Services, 246, 295 Lidocaine, 90, 154, 172, 295 Ligament, 181, 295, 317, 328 Ligands, 47, 196, 295 Ligation, 51, 295 Limbic, 254, 295, 296, 315 Limbic System, 254, 296, 315 Linkages, 61, 287, 296 Lipid, 149, 163, 193, 267, 292, 294, 296, 301 Lipid Peroxidation, 163, 296 Lithium, 257, 296 Lobe, 254, 256, 265, 296, 316 Localization, 51, 290, 296 Localized, 34, 167, 171, 262, 282, 287, 291, 296, 300, 302, 313, 323, 331, 335 Locomotion, 296, 313 Locomotor, 30, 296 Longitudinal study, 26, 34, 56, 296 Long-Term Care, 238, 296 Long-Term Potentiation, 38, 296 Loop, 287, 296 Low Back Pain, 16, 19, 22, 28, 127, 180, 296 Luciferase, 53, 296 Lumbar, 93, 166, 259, 265, 292, 296, 297, 323, 332
Lumbosacral Plexus, 166, 297 Lupus, 297, 330 Luteal Phase, 58, 297 Luxation, 276, 297 Lymph, 208, 266, 279, 297 Lymph node, 266, 297 Lymphatic, 7, 279, 291, 297, 313, 327, 332 Lymphedema, 50, 208, 297 Lymphocyte, 256, 297, 298 Lymphoid, 143, 256, 297 M Magnetic Resonance Imaging, 297 Malformation, 84, 297 Malignancy, 44, 297 Malignant, 7, 44, 63, 77, 97, 133, 257, 297, 303, 319 Malingering, 156, 297 Malnutrition, 165, 195, 258, 297 Mandibular Nerve, 297, 334 Mania, 159, 168, 182, 297, 298 Manic, 257, 261, 296, 298, 318 Manic-depressive psychosis, 298, 318 Manifest, 259, 298 Mastication, 297, 298, 334 Mastitis, 298, 325 Matrix metalloproteinase, 181, 298 Maxillary, 298, 334 Medial, 41, 298, 307, 332 Median Nerve, 264, 298 Mediate, 9, 43, 56, 165, 184, 193, 196, 276, 298 Mediator, 39, 52, 155, 266, 298, 324 Medical Staff, 277, 298 Medicament, 159, 298, 329 MEDLINE, 231, 298 Medullary, 45, 93, 275, 298 Meiosis, 298, 330 Melanin, 298, 311, 335 Membrane Glycoproteins, 298 Membrane Proteins, 184, 298 Memory, 60, 72, 77, 274, 296, 298 Meninges, 265, 272, 277, 299, 327 Menopause, 31, 299, 314, 316 Menstrual Cycle, 31, 58, 98, 282, 297, 299, 315 Menstruation, 236, 253, 282, 297, 299, 315 Mental Disorders, 110, 144, 299, 317, 318 Mental Health, iv, 5, 18, 111, 118, 144, 211, 230, 232, 236, 299, 318 Mental Processes, 276, 299, 317 Mentors, 27, 299 Meperidine, 36, 151, 168, 299
Index 349
Mesencephalic, 299, 334 Mesolimbic, 257, 299 Metabolite, 151, 160, 176, 275, 299, 306, 315 Metabotropic, 165, 196, 299 Metastasis, 298, 299, 303 Metastatic, 7, 299 Methionine, 260, 275, 299, 316 MI, 111, 146, 147, 150, 159, 169, 191, 196, 197, 250, 299 Microbe, 299, 333 Microbiology, 251, 258, 299 Microdialysis, 51, 299 Microorganism, 268, 299, 337 Micturition, 42, 300 Migration, 199, 300 Milligram, 220, 300 Mineralocorticoids, 252, 272, 300 Mitral Valve, 182, 300 Mitral Valve Prolapse, 182, 300 Mobilization, 93, 123, 300 Modeling, 47, 300 Modification, 118, 125, 163, 178, 237, 284, 300, 319 Modulator, 41, 43, 300 Molecular, 8, 31, 37, 47, 48, 59, 60, 79, 91, 105, 123, 168, 174, 181, 231, 233, 261, 263, 270, 282, 300, 316, 320, 334, 335 Molecular Structure, 300, 334 Monitor, 18, 21, 43, 60, 212, 300, 306 Monoamine, 51, 159, 176, 254, 275, 300, 335 Monoamine Oxidase, 254, 275, 300, 335 Monocytes, 292, 295, 300, 313 Mononuclear, 300, 301, 334 Morphological, 8, 278, 301 Motility, 188, 291, 301, 324 Motion Sickness, 301, 302 Motor Activity, 271, 301, 318 Motor nerve, 153, 301, 310 Motor Neurons, 38, 301 Movement Disorders, 55, 67, 257, 301 Mucinous, 283, 301 Mucins, 301, 323 Mucosa, 152, 266, 297, 301 Multiple sclerosis, 154, 164, 198, 199, 301 Muscarinic Agonists, 267, 301 Muscle relaxant, 161, 190, 301, 303, 318 Muscle Spasticity, 154, 301 Muscle tension, 90, 301 Muscular Diseases, 301, 304, 309, 318 Muscular Dystrophies, 277, 301
Musculoskeletal Diseases, 202, 301 Myasthenia, 301, 303, 318 Mydriatic, 275, 301 Myelin, 174, 274, 301, 306 Myelin Sheath, 174, 301, 306 Myocardial infarction, 272, 299, 302, 316 Myocardium, 255, 299, 302 Myoclonus, 165, 195, 302 Myosin, 263, 302 N Nafarelin, 24, 302 Naive, 30, 302 Naloxone, 50, 260, 302 Naltrexone, 14, 302 Narcolepsy, 160, 176, 183, 275, 302 Narcosis, 302 Narcotic, 45, 47, 151, 168, 179, 202, 280, 282, 288, 295, 299, 301, 302, 308, 316, 333 Nausea, 23, 127, 161, 187, 190, 256, 257, 276, 302, 309, 315 NCI, 1, 143, 229, 268, 302 Neck Pain, 203, 302 Necrosis, 265, 291, 299, 302, 303 Neonatal, 35, 303 Neoplasms, 164, 257, 303, 319 Neoplastic, 255, 281, 288, 303 Neostigmine, 303, 318 Nerve Endings, 39, 173, 184, 191, 286, 303, 305 Nerve Fibers, 166, 262, 303, 327, 332 Nerve Growth Factor, 15, 30, 56, 303, 305 Nervous System Diseases, 54, 303 Nervousness, 161, 303 Networks, 240, 303 Neural Pathways, 153, 158, 303 Neuralgia, 8, 66, 180, 198, 207, 303, 314 Neurites, 39, 303 Neurodegenerative Diseases, 146, 148, 150, 165, 195, 196, 259, 303 Neuroeffector Junction, 303, 304 Neuroendocrine, 50, 108, 125, 304 Neurogenic, 40, 42, 193, 304 Neuroleptic, 253, 257, 304 Neurologic, 154, 165, 167, 196, 304, 333 Neuromuscular, 251, 303, 304, 309, 318, 331 Neuromuscular Diseases, 304, 309, 318 Neuromuscular Junction, 251, 303, 304 Neuronal, 8, 15, 21, 30, 31, 35, 37, 38, 40, 41, 52, 62, 66, 67, 79, 147, 148, 150, 156, 163, 165, 172, 173, 176, 187, 188, 190,
350 Chronic Pain
191, 195, 196, 197, 259, 263, 268, 302, 304, 310 Neuropathy, 39, 53, 66, 166, 172, 176, 189, 196, 198, 218, 304, 310, 323 Neuropeptide, 6, 56, 304 Neurophysiology, 107, 124, 274, 304 Neuroprotective Agents, 146, 147, 170, 186, 197, 304 Neuropsychological Tests, 22, 304 Neuroretinitis, 304, 322 Neurosis, 304, 305, 311 Neurosurgeon, 54, 304 Neurosurgery, 21, 55, 67, 74, 89, 93, 106, 115, 126, 207, 304 Neurotic, 189, 305 Neurotoxicity, 149, 162, 186, 275, 294, 305 Neurotoxin, 15, 305 Neurotrophins, 42, 305 Neutropenia, 305, 313 Neutrophils, 285, 295, 305, 313 Niacin, 158, 305, 334 Niche, 6, 305 Nicotine, 160, 176, 183, 190, 305 Nitric Oxide, 29, 38, 45, 63, 181, 305 Nitrogen, 179, 253, 254, 255, 281, 282, 285, 305, 334 Nociceptors, 38, 166, 185, 199, 305 Nonmalignant, 52, 305 Nonverbal Communication, 305, 318 Norepinephrine, 159, 176, 184, 252, 254, 276, 286, 305, 325, 329 Norethindrone, 65, 306 Normal Distribution, 66, 306 Nortriptyline, 26, 306 Noscapine, 151, 306 Nuclear, 259, 278, 280, 283, 296, 303, 306, 331 Nuclei, 181, 254, 256, 278, 284, 296, 297, 306, 307, 317, 334, 336 Nucleic acid, 185, 187, 188, 198, 284, 288, 290, 305, 306 Nucleic Acid Hybridization, 288, 306 O Occupational Therapy, 237, 239, 306 Odour, 258, 306 Ointments, 266, 276, 306 Oligodendroglia, 302, 306 Oncologist, 32, 306 Oncology, 114, 214, 306 Opacity, 274, 306 Operon, 306, 321 Ophthalmic, 307, 334
Opioid Peptides, 31, 45, 277, 307 Opium, 151, 301, 306, 307, 309 Opsin, 307, 322 Optic Chiasm, 289, 307, 329 Optic Disk, 275, 307 Optic Nerve, 304, 307, 322 Orgasm, 278, 307 Orofacial, 37, 48, 97, 167, 281, 307 Orthostatic, 168, 257, 307 Osmosis, 307 Osmotic, 98, 307 Osteoarthritis, 23, 57, 83, 109, 111, 127, 166, 176, 180, 183, 196, 239, 307 Osteoporosis, 164, 307 Outpatient, 85, 201, 307 Ovarian Follicle, 272, 307 Ovaries, 308, 321, 325, 331 Ovary, 272, 285, 307, 308 Overdosage, 175, 308 Overdose, 271, 308 Ovulation, 282, 297, 306, 308 Ovum, 272, 284, 307, 308, 315, 337 Oxalate, 146, 308 Oxidation, 153, 154, 251, 257, 273, 296, 308 Oxycodone, 151, 152, 174, 308 Oxygenase, 29, 308 Oxygenation, 287, 308 Oxytocic, 308, 326 P Pacemaker, 57, 308 Pain Measurement, 155, 308 Pain Threshold, 26, 308 Pain, Postoperative, 180, 308 Painful bladder syndrome, 7, 308 Palliative, 7, 308, 331 Palpation, 58, 308 Palsy, 157, 308 Pancreas, 7, 251, 260, 275, 292, 309, 334 Pancreatic, 7, 266, 282, 309 Pancreatic cancer, 7, 309 Panic, 178, 309 Panic Disorder, 178, 309 Papaverine, 151, 307, 309 Paraganglia, Chromaffin, 267, 309 Paralysis, 59, 262, 272, 299, 309, 318, 327, 331 Paraplegia, 43, 126, 309 Parasitic, 260, 309 Paresthesia, 153, 309, 331 Parkinsonism, 146, 147, 150, 170, 197, 257, 309 Paroxysmal, 255, 279, 286, 309
Index 351
Particle, 309, 326, 333 Parturition, 181, 309 Patch, 6, 21, 33, 38, 46, 90, 142, 174, 309, 333 Pathogenesis, 42, 163, 309 Pathologic, 38, 163, 167, 261, 262, 271, 289, 309, 325, 327, 335 Pathophysiology, 19, 48, 98, 186, 192, 212, 310 Patient Education, 5, 69, 236, 244, 246, 250, 310 Patient Selection, 4, 310 Pelvic, 7, 24, 25, 40, 42, 65, 152, 279, 310, 317 Penicillin, 256, 310 Penis, 278, 310 Pensions, 110, 310 Peptide, 6, 14, 46, 56, 62, 91, 181, 189, 193, 260, 266, 307, 310, 314, 316, 317, 332 Perception, 6, 15, 32, 33, 41, 48, 58, 67, 68, 79, 86, 98, 99, 153, 155, 190, 199, 270, 274, 310, 323 Percutaneous, 28, 174, 310, 311 Perfusion, 78, 282, 290, 310 Pericardium, 310, 330 Perinatal, 146, 147, 150, 170, 197, 310 Peripheral blood, 40, 310 Peripheral Nerves, 66, 153, 155, 167, 303, 310, 314, 327 Peripheral Nervous System Diseases, 304, 309, 310, 318 Peripheral Neuropathy, 53, 56, 310 Peroneal Nerve, 310, 323 Petrolatum, 278, 311 PH, 85, 120, 311 Pharmaceutical Preparations, 162, 265, 280, 284, 311 Pharmaceutical Solutions, 277, 311 Pharmacists, 84, 85, 311 Pharmacodynamics, 98, 149, 311 Pharmacokinetic, 149, 311 Pharmacologic, 5, 8, 28, 32, 45, 51, 67, 163, 167, 171, 178, 182, 215, 255, 258, 286, 311, 333 Pharmacotherapy, 72, 81, 118, 311 Phenolphthalein, 278, 311 Phenyl, 179, 299, 311 Phenylalanine, 131, 311, 335 Phobia, 98, 311 Phobic Disorders, 311 Phonophoresis, 293, 311 Phosphodiesterase, 176, 194, 311
Phosphodiesterase Inhibitors, 176, 311 Phospholipases, 312, 325 Phosphorus, 263, 312 Phosphorylated, 60, 312 Phosphorylates, 60, 312 Phosphorylation, 38, 61, 312 Phototherapy, 312, 323 Phototransduction, 312, 323 Physical Examination, 5, 41, 42, 312 Physical Fitness, 280, 312 Physical Therapy, 5, 23, 26, 28, 67, 141, 237, 312 Physiologic, 15, 33, 40, 163, 182, 253, 261, 286, 294, 299, 302, 312, 316, 320, 324, 334 Physiology, 19, 43, 48, 55, 181, 259, 278, 304, 312 Pigments, 264, 312, 322 Pilot study, 15, 27, 47, 100, 103, 115, 123, 218, 312 Pineal Body, 312 Pineal gland, 57, 312 Piperidines, 170, 191, 192, 312 Pituitary Gland, 272, 285, 312, 315 Placebo Effect, 23, 312 Placenta, 312, 315 Plague, 53, 313 Plants, 151, 175, 251, 253, 260, 267, 268, 280, 285, 295, 306, 312, 313, 323, 333, 334 Plasma, 12, 63, 199, 253, 256, 265, 282, 284, 285, 287, 300, 313, 317, 324 Plasma cells, 256, 313 Plasmids, 13, 313 Plasticity, 37, 43, 123, 313 Platelet Activating Factor, 163, 313 Platelet Activation, 313, 325 Platelet Aggregation, 255, 305, 313, 332 Platelets, 305, 313, 332 Plexus, 166, 262, 297, 313, 323 Pneumothorax, 87, 313 Poisoning, 166, 196, 208, 274, 293, 302, 313 Polymerase, 313, 321 Polymers, 164, 313, 317 Polymorphic, 273, 313 Polymorphism, 29, 273, 313 Polyneuropathies, 164, 314 Polypeptide, 42, 180, 181, 185, 254, 269, 282, 288, 314, 317, 337 Polysaccharide, 63, 256, 265, 314 Posterior, 155, 166, 254, 259, 265, 267, 276, 284, 302, 309, 312, 314, 323 Postherpetic Neuralgia, 8, 10, 39, 314 Postmenopausal, 307, 314
352 Chronic Pain
Postnatal, 35, 314 Postoperative, 11, 51, 53, 65, 141, 299, 314 Postoperative Period, 11, 314 Postsynaptic, 61, 159, 163, 165, 191, 196, 304, 314, 325, 330 Post-traumatic, 163, 286, 301, 314 Potassium, 21, 187, 188, 276, 300, 314, 319 Potentiate, 314, 315 Potentiating, 254, 314 Potentiation, 296, 314, 325 Practicability, 314, 334 Practice Guidelines, 69, 77, 83, 232, 237, 314 Preclinical, 14, 28, 192, 314 Precursor, 43, 257, 267, 276, 277, 279, 305, 311, 314, 315, 317, 334, 335 Pre-eclamptic, 277, 314 Prefrontal Cortex, 78, 114, 315 Premenstrual, 160, 175, 176, 178, 183, 236, 315 Premenstrual Syndrome, 160, 175, 176, 183, 236, 315 Prescription drug abuse, 18, 315 Presynaptic, 61, 159, 163, 303, 304, 315, 330 Presynaptic Terminals, 303, 315, 330 Prevalence, 3, 4, 10, 16, 25, 31, 44, 48, 64, 99, 173, 220, 315 Probe, 61, 299, 315 Problem Solving, 104, 315 Procaine, 295, 315 Prodrug, 171, 315 Progesterone, 31, 58, 306, 315, 328 Progression, 255, 315 Progressive, 49, 60, 265, 274, 277, 279, 285, 301, 303, 307, 313, 315, 321, 335 Projection, 33, 173, 274, 305, 307, 315 Proline, 269, 289, 315 Promoter, 21, 315 Prone, 34, 53, 60, 315 Pro-Opiomelanocortin, 307, 315 Propafenone, 172, 316 Prophase, 316, 330 Prophylaxis, 156, 162, 164, 316, 322 Propionic Acids, 221, 316 Propoxyphene, 151, 316 Propranolol, 160, 184, 316 Prospective study, 296, 316 Prostaglandin, 38, 255, 273, 316, 332 Prostaglandin-Endoperoxide Synthase, 273, 316 Prostaglandins A, 291, 316
Prostate, 164, 260, 316, 334 Protective Agents, 150, 263, 317 Protein C, 36, 193, 194, 254, 259, 317 Protein Conformation, 254, 317 Protein Kinases, 194, 317 Protein S, 36, 59, 194, 210, 261, 284, 317, 322 Protein Subunits, 36, 317 Proteolytic, 253, 269, 282, 317 Prothrombin, 317, 332 Protocol, 10, 17, 24, 28, 57, 142, 317 Protons, 288, 293, 317, 319 Proximal, 276, 314, 315, 317 Psychiatric, 73, 102, 119, 157, 159, 178, 208, 299, 317 Psychiatry, 16, 18, 22, 72, 79, 86, 105, 109, 111, 115, 178, 282, 317, 329 Psychic, 304, 317, 318, 324 Psychogenic, 160, 161, 317 Psychological Techniques, 203, 317 Psychomotor, 264, 274, 304, 318 Psychopathology, 80, 318 Psychosis, 146, 147, 150, 165, 170, 191, 195, 196, 197, 209, 257, 318 Psychosomatic, 18, 93, 100, 105, 123, 318 Psychotherapy, 19, 20, 99, 269, 318, 320 Psychotomimetic, 254, 275, 318 Psychotropic, 83, 162, 163, 318 Puberty, 64, 302, 318 Public Health, 20, 23, 24, 25, 52, 82, 83, 211, 232, 318 Public Policy, 231, 318 Publishing, 69, 71, 73, 82, 119, 121, 206, 208, 318 Pulmonary, 54, 146, 147, 150, 170, 197, 261, 280, 282, 295, 318, 332, 336 Pulmonary Artery, 261, 318, 336 Pulse, 300, 318 Pupil, 271, 275, 301, 318 Pyridostigmine Bromide, 35, 318 Q Quadriplegia, 43, 318 Quality of Life, 25, 28, 31, 35, 44, 45, 50, 52, 57, 90, 105, 110, 134, 135, 136, 173, 319 Quinidine, 151, 319 Quinine, 319 R Race, 160, 176, 183, 184, 218, 300, 319 Radiation, 255, 259, 282, 283, 293, 306, 319, 337 Radiation oncologist, 306, 319 Radiation therapy, 282, 319
Index 353
Radicular, 19, 319 Radiculopathy, 319, 323 Radioactive, 259, 286, 288, 290, 293, 306, 319 Radioimmunotherapy, 319, 320 Radiological, 310, 319 Radiopharmaceutical, 284, 319 Radiotherapy, 7, 319 Random Allocation, 320 Randomization, 17, 65, 85, 320 Randomized clinical trial, 34, 35, 49, 56, 57, 64, 320 Randomized Controlled Trials, 17, 320 Reactivation, 10, 320 Reagent, 254, 297, 320 Reality Testing, 318, 320 Reassurance, 202, 320 Receptor, 8, 9, 13, 16, 29, 31, 36, 37, 38, 41, 42, 46, 48, 60, 61, 62, 146, 147, 148, 150, 159, 163, 165, 168, 169, 170, 177, 179, 180, 181, 184, 187, 188, 189, 190, 191, 192, 193, 194, 196, 197, 198, 251, 256, 266, 270, 275, 276, 294, 299, 320, 324, 325 Receptors, Serotonin, 320, 324 Recombinant, 29, 46, 60, 156, 161, 198, 320, 336 Recombinant Proteins, 60, 320 Rectal, 221, 320 Rectum, 257, 261, 275, 283, 291, 295, 317, 320, 329 Recur, 321, 323 Recurrence, 24, 65, 261, 298, 321, 323 Red blood cells, 47, 279, 308, 321, 323 Refer, 1, 269, 276, 282, 287, 296, 302, 303, 304, 306, 318, 319, 321 Reflex, 8, 19, 42, 129, 157, 160, 183, 236, 281, 321 Refraction, 321, 327 Refractory, 8, 10, 13, 28, 45, 55, 59, 102, 183, 201, 321 Regeneration, 59, 321 Regimen, 4, 53, 65, 143, 161, 168, 182, 268, 277, 311, 312, 321 Regurgitation, 300, 321 Relapse, 203, 321 Relaxant, 309, 321 Relaxation Techniques, 118, 119, 129, 321 Relaxin, 181, 321 Reliability, 73, 102, 107, 321 Remission, 261, 298, 321 Renal failure, 274, 321 Repressor, 55, 306, 321
Research Design, 22, 24, 40, 321 Research Support, 7, 27, 321 Respiration, 257, 266, 271, 272, 300, 321 Response rate, 7, 321 Restoration, 43, 59, 74, 103, 312, 320, 321, 337 Retina, 267, 275, 304, 307, 312, 322 Retinal, 186, 270, 275, 307, 312, 322 Retinitis, 146, 147, 150, 165, 170, 191, 195, 197, 322 Retinoids, 322, 337 Retinol, 322 Retrograde, 30, 322 Retrospective, 12, 101, 322 Rheumatism, 154, 322 Rheumatoid, 135, 164, 167, 180, 183, 186, 189, 199, 322 Rheumatoid arthritis, 164, 183, 186, 189, 199, 322 Rhinitis, 322, 325 Ribonucleoside Diphosphate Reductase, 289, 322 Ribose, 251, 322 Ribosome, 322, 333 Rigidity, 289, 309, 313, 322 Risk factor, 7, 10, 25, 40, 54, 57, 64, 316, 322 Rod, 108, 125, 268, 322 Rural Population, 70, 323 S Salicylate, 266, 323 Salicylic, 323 Salicylic Acids, 323 Saliva, 58, 323 Salivary, 59, 273, 275, 309, 323 Salivary glands, 273, 275, 323 Saponins, 323, 328 Schizoid, 323, 337 Schizophrenia, 165, 178, 186, 195, 278, 323, 337 Schizotypal Personality Disorder, 274, 323, 337 Sciatic Nerve, 39, 41, 51, 310, 323, 332 Sciatica, 158, 323 Scleroderma, 181, 323 Sclerosis, 148, 150, 154, 164, 165, 166, 172, 186, 195, 196, 197, 301, 323 Screening, 135, 180, 181, 198, 199, 208, 268, 323 Seasonal Affective Disorder, 160, 183, 323 Second Messenger Systems, 6, 305, 323
354 Chronic Pain
Secretion, 43, 57, 199, 272, 275, 284, 285, 288, 289, 292, 294, 300, 301, 323, 324 Secretory, 267, 304, 324, 330 Secretory Vesicles, 267, 324 Sedative, 17, 169, 177, 254, 259, 268, 280, 324 Sedentary, 15, 324 Seizures, 149, 166, 182, 196, 264, 274, 309, 324, 328 Self Care, 58, 64, 251, 324 Semen, 278, 317, 324 Senile, 307, 324 Sensibility, 254, 289, 324 Sensitization, 31, 34, 35, 38, 40, 42, 48, 53, 60, 62, 86, 187, 190, 324 Sensory Thresholds, 50, 324 Septicaemia, 324, 325 Sequela, 43, 198, 324 Sequence Homology, 187, 188, 324 Serotonin Agonists, 324, 325 Serotonin Antagonists, 163, 325 Serotypes, 21, 325 Serum, 255, 257, 269, 285, 290, 294, 300, 325, 334 Sex Characteristics, 252, 255, 318, 325 Shock, 169, 255, 278, 302, 325, 334 Shoulder Pain, 240, 325 Sibutramine, 176, 325 Signal Transduction, 36, 194, 263, 292, 325 Signs and Symptoms, 321, 325 Skeletal, 161, 180, 190, 255, 268, 272, 294, 301, 319, 325, 326 Skeleton, 294, 316, 325 Skull, 272, 325, 331 Sleep apnea, 325, 329 Small intestine, 277, 288, 291, 292, 326 Smooth muscle, 43, 181, 184, 255, 258, 262, 263, 271, 288, 301, 309, 326, 329 Social Environment, 319, 326 Social Support, 66, 104, 326, 328 Sodium, 59, 66, 69, 172, 187, 188, 192, 276, 300, 312, 319, 326 Sodium Channels, 59, 66, 69, 192, 312, 319, 326 Solitary Nucleus, 259, 326 Solvent, 260, 280, 307, 311, 326 Soma, 20, 59, 326 Somatic, 8, 26, 33, 42, 66, 77, 252, 272, 284, 296, 298, 310, 315, 326 Sorbitol, 288, 326 Sound wave, 270, 326 Sparteine, 151, 326
Spasm, 150, 161, 165, 195, 197, 257, 271, 299, 304, 326 Spastic, 293, 326 Spasticity, 54, 153, 166, 289, 326, 327 Spatial disorientation, 276, 327 Specialist, 241, 275, 327 Specificity, 9, 41, 107, 253, 263, 327 Spectrum, 37, 63, 69, 186, 190, 210, 211, 327 Sphincter, 8, 87, 327 Spike, 67, 327 Spinal Cord Diseases, 309, 318, 327 Spinal Cord Injuries, 126, 141, 142, 319, 327 Spinal Nerve Roots, 319, 323, 327 Spinal Nerves, 310, 327 Spleen, 273, 297, 327 Splint, 12, 327 Spondylitis, 87, 327 Sporadic, 303, 328 Sprains and Strains, 296, 328 Stabilizer, 30, 328 Staging, 54, 328 Status Epilepticus, 146, 147, 150, 170, 197, 328 Steel, 268, 328 Stellate, 101, 328 Stellate Ganglion, 101, 328 Sterility, 291, 328 Steroid, 58, 163, 272, 323, 328 Stimulant, 168, 254, 263, 275, 288, 294, 328 Stomach, 189, 190, 251, 275, 280, 283, 288, 302, 326, 327, 328 Stool, 291, 293, 295, 328 Stress management, 66, 203, 328 Striatum, 54, 328 Stromal, 279, 328 Strychnine, 149, 191, 328 Stump, 198, 329 Stupor, 295, 302, 329 Subacute, 67, 291, 329 Subarachnoid, 45, 161, 286, 329 Subclinical, 291, 324, 329 Subliminal, 33, 329 Subspecies, 327, 329 Substance P, 15, 40, 51, 299, 324, 329 Substrate, 273, 329, 335 Sufentanil, 98, 329 Sumatriptan, 221, 329 Support group, 203, 240, 329 Suppositories, 221, 284, 329 Suppression, 41, 55, 272, 329
Index 355
Suprachiasmatic Nucleus, 57, 329 Supraspinal, 50, 54, 329 Sympathetic Nervous System, 184, 255, 259, 267, 304, 329 Sympatholytics, 221, 329 Sympathomimetic, 254, 275, 276, 279, 294, 306, 329, 335 Symphysis, 317, 330 Symptomatic, 11, 24, 157, 330 Symptomatic treatment, 158, 330 Symptomatology, 14, 138, 330 Synapses, 155, 296, 304, 305, 327, 330 Synapsis, 330 Synaptic, 37, 157, 159, 165, 196, 296, 305, 325, 330 Synaptic Transmission, 165, 196, 305, 330 Synaptic Vesicles, 330 Synergistic, 11, 28, 38, 330 Synovial, 63, 330 Systemic, 40, 51, 72, 142, 164, 224, 255, 261, 262, 274, 279, 291, 293, 313, 319, 323, 330, 333 Systemic lupus erythematosus, 72, 330 Systole, 300, 330 Systolic, 289, 300, 330 T T cell, 47, 330 Tardive, 257, 330 Telecommunications, 331 Telemedicine, 104, 331 Temporal, 26, 59, 60, 67, 137, 254, 286, 331, 334 Tendonitis, 158, 331 Tetani, 331 Tetanic, 331 Tetanus, 182, 331 Tetracaine, 88, 331 Tetrahydrocannabinol, 163, 263, 331 Tetrodotoxin, 8, 69, 331 Thalamic, 36, 67, 331 Thalamus, 26, 35, 41, 51, 67, 93, 155, 166, 262, 275, 296, 315, 331 Therapeutics, 52, 53, 62, 73, 90, 98, 120, 124, 159, 161, 186, 224, 300, 331 Thermal, 15, 30, 50, 60, 63, 66, 67, 154, 166, 183, 185, 199, 276, 331 Thigh, 285, 331 Thiourea, 188, 189, 331 Third Ventricle, 289, 312, 331 Thoracic, 72, 87, 259, 262, 298, 328, 332 Thoracic Surgery, 72, 87, 332 Thorax, 251, 297, 332
Threshold, 39, 57, 65, 173, 180, 280, 289, 329, 332 Thrombin, 194, 282, 313, 317, 332 Thrombocytopenia, 313, 332 Thrombomodulin, 317, 332 Thrombosis, 194, 293, 317, 328, 332 Thromboxanes, 257, 273, 278, 332 Thrombus, 272, 291, 294, 313, 332 Thymus, 290, 297, 332 Thyroid, 289, 332, 335 Thyrotropin, 289, 332 Tibial Nerve, 323, 332 Time Management, 328, 332 Tin, 153, 264, 309, 310, 332 Tinnitus, 3, 39, 212, 218, 332, 336 Tissue, 8, 11, 13, 28, 31, 37, 39, 40, 45, 48, 56, 63, 152, 153, 154, 161, 164, 167, 181, 184, 185, 186, 190, 198, 253, 255, 256, 258, 260, 261, 262, 263, 264, 266, 271, 275, 277, 278, 279, 281, 282, 283, 285, 287, 289, 290, 291, 292, 293, 295, 297, 298, 302, 303, 304, 305, 310, 312, 313, 321, 322, 325, 326, 328, 330, 332, 333, 334, 335, 337 Tissue Culture, 303, 333 Tomography, 26, 333 Tonic, 271, 333 Tonicity, 277, 294, 333 Tooth Preparation, 251, 333 Topical, 4, 183, 221, 280, 288, 311, 333 Toxic, iv, 28, 42, 260, 272, 273, 287, 290, 304, 305, 333 Toxicity, 11, 13, 277, 333 Toxicology, 6, 14, 108, 232, 333 Toxins, 256, 263, 291, 319, 333 Trace element, 267, 332, 333 Traction, 268, 333 Tramadol, 4, 77, 87, 333 Transcutaneous, 5, 71, 119, 125, 135, 157, 237, 333 Transdermal, 73, 174, 218, 219, 224, 333 Transduction, 13, 21, 29, 38, 173, 194, 325, 333 Transfection, 261, 333 Transfer Factor, 290, 333 Transient Ischemic Attacks, 157, 333 Translation, 181, 333 Translational, 37, 39, 51, 334 Transmitter, 61, 251, 258, 276, 280, 293, 298, 305, 330, 334, 335 Transplantation, 10, 45, 166, 290, 334
356 Chronic Pain
Treatment Outcome, 19, 71, 90, 134, 136, 137, 138, 334 Tremor, 153, 157, 299, 309, 334 Tricyclic, 13, 167, 190, 198, 221, 254, 334 Trigeminal, 8, 66, 174, 207, 281, 297, 334 Trigeminal Ganglion, 66, 334 Trigeminal Nerve, 334 Trigeminal Nuclei, 174, 334 Trigger zone, 257, 334 Tropism, 21, 334 Tryptophan, 269, 324, 334 Tumor marker, 260, 334 Tumor Necrosis Factor, 6, 334 Tumour, 283, 335 Tyramine, 260, 300, 335 Tyrosine, 42, 194, 276, 335 U Ulcer, 277, 335 Ulceration, 187, 335 Unconscious, 255, 274, 290, 335 Ureters, 294, 335 Urethra, 8, 310, 316, 335 Urinary tract, 42, 118, 275, 335 Urinate, 335, 337 Urine, 58, 261, 263, 276, 289, 291, 294, 300, 308, 335 Urogenital, 180, 284, 335 Urothelium, 43, 335 Uterus, 266, 272, 278, 279, 282, 283, 290, 299, 308, 315, 335 V Vaccine, 252, 317, 335 Varicella, 10, 335 Vascular, 54, 191, 198, 255, 263, 266, 267, 279, 286, 291, 305, 307, 312, 327, 332, 335 Vasculitis, 266, 335 Vasoconstriction, 279, 335 Vasodilatation, 279, 335 Vasodilation, 255, 309, 335 Vasodilator, 256, 262, 276, 288, 309, 335 VE, 84, 335 Vector, 21, 29, 46, 333, 335 Veins, 261, 266, 313, 336 Venom, 9, 336 Venous, 258, 261, 265, 287, 293, 317, 336 Venous blood, 261, 265, 336 Ventral, 38, 51, 153, 289, 327, 336
Ventricle, 254, 300, 318, 330, 331, 336 Ventricular, 316, 336 Venules, 261, 336 Vertebrae, 292, 327, 336 Vertebral, 74, 153, 198, 239, 279, 336 Vesicular, 288, 336 Vestibule, 268, 336 Vestibulocochlear Nerve, 258, 332, 336 Vestibulocochlear Nerve Diseases, 332, 336 Veterinary Medicine, 231, 336 Viral, 21, 46, 164, 199, 333, 336 Viral vector, 21, 46, 336 Virulence, 333, 336 Virus, 10, 28, 46, 118, 150, 161, 197, 259, 265, 279, 284, 330, 333, 336, 337 Viscera, 326, 337 Visceral, 7, 34, 35, 48, 63, 167, 259, 272, 284, 296, 337 Visceral Afferents, 259, 284, 337 Viscosity, 164, 337 Vitamin A, 202, 292, 322, 337 Vitreous Hemorrhage, 275, 337 Vitro, 337 Vivo, 13, 14, 21, 37, 51, 337 Void, 52, 337 Volition, 193, 293, 337 Voltage-gated, 59, 337 Vomica, 328, 337 W Wakefulness, 193, 274, 337 Weight Gain, 176, 323, 337 White blood cell, 256, 295, 297, 305, 313, 330, 337 Withdrawal, 38, 46, 61, 146, 147, 150, 151, 170, 191, 197, 274, 299, 337 Wound Healing, 298, 337 Wounds, Gunshot, 327, 337 X Xenograft, 255, 337 X-ray, 15, 264, 270, 283, 306, 319, 328, 337 Z Ziconotide, 98, 142, 337 Zoster, 10, 337 Zygote, 270, 337 Zymogen, 317, 337
Index 357
358 Chronic Pain
Index 359
360 Chronic Pain
