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VOLUME 2 NUMBER 2 2008
Advances in PAIN MANAGEMENT
Editor-in-Chief Ricardo Cruciani, New York, NY, USA
Associate Editors Russell Portenoy, New York, NY, USA Steven D Passik, New York, NY, USA
Methods for Monitoring Medication Use in Chronic Pain Patients Robert J Gatchel
Treatment Selection in Substance Abusers with Pain Jeanne M Manubay, Sandra D Comer, and Maria A Sullivan
Risk Assessment for Opiod Misuse in Chronic Pain Treatment Michael F Weaver and Sidney H Schnoll
CASE STUDY Patient Affected by Severe Cancer Pain and Treated with Combined Strong Opioids Elena Catala, Analia Azaro, and Marta Ferrandiz
www.advancesinpainmanagement.com
Jointly sponsored by the University of Kentucky Colleges of Pharmacy and Medicine and Remedica Medical Education and Publishing. This journal is supported by an The University of Kentucky is an equal opportunity university. educational grant from Cephalon RT379_4_REM_PAIN_COV_03.qxd 10/7/08 1:35 PM Page 2
Advances in Pain Management is supported by an educational grant from Cephalon.
Faculty Disclosures The following are relevant financial relationships declared by the journal’s Editor-in-Chief, Associate Editor, Editors, and Advisory Board Members: Ricardo A Cruciani: Merck, Pfizer. Steven D Passik: Cephalon, Ligand, Lilly, Pricara, King Pharmaceuticals. Russell K Portenoy: Abbott, Adolor, Alpharma, Anesiva, Archimedes Pharma, Ascent Biomedical Ventures, Aveva Drug Delivery, Baxter, Bayer, BioDelivery Sciences, Biometrix, Biovail, Cephalon, CombinatroRx, Cytogel, Endo Pharmaceuticals, Fralex, Genentech, GlaxoSmithKline, Globomax, GPC Biotech, GW Pharmaceuticals, Janssen/Ortho-McNeil, Johnson&Johnson, King Pharmaceuticals, Ligand Pharmaceuticals, Merck, Nektar Therapeutics, Neuromed, Novartis, Organon, Painceptor, Pfizer, Pharmos, PPD, Progenics, Sarentis, United Biosource Corp, Valeant Pharmaceuticals North America, Xenome, Xenon Pharmaceuticals, Wyeth. Lara Dhingra: None declared. Helena Knotkova: None declared. Miroslav Backonja: Allergen, Avanir, Eisai, GlaxoSmithKline, Johnson&Johnson, Lilly, Merck, Neurogesx, Pfizer. Peggy Compton: Pricara. Edward C Covington: Lilly, Pfizer. Robert Dworkin: Allergan, Balboa, CombinatoRx, Dara, Eli Lilly, Endo, EpiCept, Fralex, GlaxoSmithKline, GW Pharmaceuticals, KAI Pharmaceuticals, Merck, NeurogesX, Pfizer, Supernus, US Food and Drug Administration, US National Institute of Health, US Veterans Administration, Wyeth, XTL Biopharmaceuticals. Doug Gourlay: Alpharma, Cephalon, GW Pharmaceuticals, King Pharmaceuticals, Ortho-Ligant, Purdue. Martin Grabois: None declared. Francis Keefe: None declared.Jianren Mao: None declared. Judith A Paice: Dendreon, Endo, ExcelleRx, GlaxoSmithKline. Neal Slatkin: Bioscience Delivery, Cephalon, KV Pharmaceutical, Ortho Biotech, Pfizer, Valeant, Wyeth. Editorial Policy Advances in Pain Management is an independent journal published by Remedica Medical Education and Publishing. Editorial control is vested entirely in the Editor-in-Chief, Associate Editor, Editors, and Editorial Advisory Board. Before publication, all material submitted to the journal is subjected to rigorous review by the Editor-in-Chief, Associate Editor, Editors, Editorial Advisory Board, and/or independent reviewers for suitability of scientific and medical content, accuracy, quality, and conflict of interest. Aims and Scope Advances in Pain Management is designed to bring a critical analysis of the world pain medicine literature, to an international, multidisciplinary audience. Our mission is to promote a better understanding of pain medicine by providing an active forum for the discussion of clinical and healthcare issues. Leading Articles – These major review articles are chosen to reflect topical clinical and healthcare issues in pain medicine. All contributions undergo a strict editorial review process. Clinical Reviews – The most important articles from the best of the international literature on pain medicine are systematically selected by the Editor-in-Chief and Associate Editor. The Editors then prepare concise and critical analyses of each article, and, most importantly, place the findings into clinical context. Meeting Reports – Advances in Pain Management also provides incisive reportage from the most important international congresses. Publisher’s Statement © Remedica Medical Education and Publishing 2008. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise without the prior permission of the copyright owners. While every effort is made by the publishers and editorial board to see that no inaccurate or misleading data, opinions, or statements appear in this journal, they wish to make it clear that the material contained in the publication represents a summary of the independent evaluations and opinions of the authors and contributors. As a consequence, the board, publishers, and any sponsoring company accept no responsibility for the consequences of any such inaccurate or misleading data or statements. Neither do they endorse the content of the publication or the use of any drug or device in a way that lies outside its current licensed application in any territory. For detailed information on any drugs or devices discussed in this publication, readers are advised to consult the Physicians Circular issued by the manufacturer. Advances in Pain Management (ISSN 1466-7401) is published four times a year. Subscriptions are available at the following rates: Europe Eur150; USA, Canada and all other territories US$200. Additional subscription information is available from the publisher. Remedica Medical Education and Publishing Ltd., 20 N. Wacker Drive, Suite 1642, Chicago, IL 60606, USA. Tel: +1 (312) 372 4020 Fax: +1 (312) 372 0217 Email: [email protected] Remedica Medical Education and Publishing Ltd., Commonwealth House, 1 New Oxford Street, London, WC1A INU, UK. Tel: +44 (0)20 7759 2999 Fax: +44 (0)20 7759 2951 Email: [email protected]
Editorial Team: Natalie Davidson, Amy Loader Editorial Manager: Scott Millar Publishers: Ian Ackland-Snow, Simon Kirsch Design and Artwork: AS&K Skylight Creative Services ISSN 1466-7401 RT379_4_REM_Pain_2_2_CME_02.qxd 10/7/08 1:22 PM Page 2 ¢ Complete the post-test answer sheet, evaluation form, and registration form, and return to: NEEDS ASSESSMENT Attn: Distance Education Advances in Pain Management, a CME-accredited UKCPMCE [MEN08061-02] educational program, systematically identifies, evaluates, and places into clinical context the most important recent One Quality Street, 6th Floor studies into the science and medicine of pain management. Lexington, KY 40507, USA It provides rapid access for busy specialists (including pain Fax: (859) 323-2920 specialists, anesthesiologists, neurologists, oncologists, general physicians, and primary care physicians) to a critical and clinically relevant review of the developments CME Alternatively, the forms can be completed on the website www.advancesinpainmanagement.com by following the links to CME. that will have most impact on their day-to-day practice Registration is required but is free to physicians and healthcare professionals. and is designed to provide management options for clinicians to allow them to better diagnose and treat CME patients suffering chronic pain. EXAMINATION ANSWERS Each issue of Advances in Pain Management will present carefully constructed leading (review) articles, written by Record your answers here by filling in the blank with the correct letter for the corresponding question: practicing pain specialists, and intended to equip readers with practical knowledge of the area under discussion. These articles are commissioned to support particular Methods for Monitoring Medication Use in Chronic Pain Patients. Robert J Gatchel educational themes identified by the Editor-in-Chief, Adv Pain Manage 2008;2(2):54–58. Editorial team, and readers. This issue of Advances in Pain 1. ____ 2. ____ 3. ____ 4. ____ 5. ____ 6. ____ Management presents three such leading articles. Treatment Selection in Substance Abusers with Pain. Steven Jeanne M Manubay, Sandra D Comer, and Maria A Sullivan. INTENDED AUDIENCE Adv Pain Manage 2008;2(2):59–67. This activity is designed to meet the educational needs of multidisciplinary clinicians and healthcare professionals 1. ____ 2. ____ 3. ____ 4. ____ 5. ____ 6. ____ involved in the care of patients with chronic pain. Risk Assessment for Opioid Misuse in Chronic Pain Treatment. Michael F Weaver and Sidney H Schnoll LEARNING OBJECTIVES Adv Pain Manage 2008;2(2):68–75. Methods for Monitoring Medication Use in Chronic Pain Patients 1. ____ 2. ____ 3. ____ 4. ____ 5. ____ 6. ____ Robert J Gatchel. Adv Pain Manage 2008;2(2):54–58. Participants will receive a confidential report of their results along with the correct answers to each question. A certificate of credit will be sent to those who Goal: To educate the reader on the best methods of assessing chronic pain patients who are at risk of successfully complete the examination with a score of 70% or higher. medication misuse or abuse. Objectives: After reading this article the reader should EVALUATION FORM STRONGLY AGREE STRONGLY DISAGREE be able to discuss: 1. The activity provided new information I had not yet acquired. 1 2 3 4 5 • Screening tools for pain-reducing medication misuse or 2. The activity helped increase my knowledge and skills. 1 2 3 4 5 abuse. • Guidelines for monitoring chronic pain patients 3. The activity content was educational and understandable. 1 2 3 4 5 undergoing opioid therapy. 4. The activity content met its objectives. 1 2 3 4 5 Treatment Selection in Substance Abusers with Pain Jeanne M Manubay, Sandra D Comer, 5. The amount of information presented was adequate for my needs. 1 2 3 4 5 and Maria A Sullivan. 6. I felt I absorbed a reasonable amount of the presented materials. 1 2 3 4 5 Adv Pain Manage 2008;2(2):59–67. Goal: To guide the reader in understanding the pain 7. The technical quality of the activity was acceptable. 1 2 3 4 5 experience in order to structure the assessment and 8. I would recommend this program to my peers. 1 2 3 4 5 treatment of pain patients. Objectives: After reading this article the reader should be 9. Funding for this activity may have come from commercial sponsors. able to discuss: Do you think you were adequately informed of commercial sponsorship or faculty conflict of interest? Yes No • Instruments for assessing the biophychosocial aspects of 10. Do you think the overall activity was biased toward certain commercial products or services? Yes No pain. • Recommended treatment selection for substance REGISTRATION FORM abusers.
Name: ...... Risk Assessment for Opioid Misuse in Chronic Pain Treatment Affiliation: ...... Michael F Weaver and Sidney H Schnoll. Adv Pain Manage 2008;2(2):68–75. Office Address: ...... Goal: To outline the best screening methods to identify ...... patients at risk of opioid misuse. Objectives: After reading this article the reader should be City: ...... State: ...... Zip Code: ...... able to discuss: Office Phone: ...... Home Phone: ...... • The use of opioids for chronic pain. • Universal precautions in chronic pain management. Email: ...... Physician License No./State: ...... Date of release: 12 October, 2008 Period of validity: 11 October, 2009 By signing this certificate, I attest that I have attended the above named continuing medical education program. Signature: ...... Credit Hours: ...... ¢
ADVANCES IN PAIN MANAGEMENT Vol 2 No 2 2008 RT379_4_REM_Pain_2_2_CME_02.qxd 10/7/08 1:22 PM Page 1 ¢ ACCREDITATION Answers should be recorded in the spaces provided overleaf This activity has been planned and implemented in One answer in correct for each question accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education Methods for Monitoring Medication Treatment Selection in Substance Abusers with Pain Risk Assessment for Opioid Misuse through the joint sponsorship of the University of Use in Chronic Pain Patients Jeanne M Manubay, Sandra D Comer, in Chronic Pain Treatment Kentucky College of Medicine and Remedica Medical Robert J Gatchel. and Maria A Sullivan. Michael F Weaver and Sidney H Schnoll. Education and Publishing. The University of Kentucky Adv Pain Manage 2008;2(2):54–58. Adv Pain Manage 2008;2(2):59–67. Adv Pain Manage 2008;2(2):68–75. College of Medicine is accredited by the ACCME to 1. When prescribing opiate prescriptions, physicians 1. Which of the following is/are aberrant drug 1. Which of the following medications has been provide continuing medical education for physicians. are legally required to do all of the following, behaviors? shown in clinical trials to be most effective for CME except: A. Forging prescriptions. treatment of neuropathic pain? The University of Kentucky College of Medicine designates A. The drug must be shown to be for justifiable B. Repeatedly seeking prescriptions from other A. Morphine. this educational activity for a maximum of two (2.0) AMA medical use. physicians or emergency rooms. B. Paroxetine. B. Patients must be assessed for possible current C. “Losing” prescribed medications on C. Duloxetine.
CME PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation addiction prior to dispensing a prescription. multiple occasions. D. Clonidine. in the activity. C. Accurate records of prescribing practices for D. Injecting oral formulations. E. Piroxicam. each patient must be kept in each patient’s E. All of the above. 2. A 36-year-old man had a motor vehicle collision The University of Kentucky College of Medicine presents chart. 2. All of the following are appropriate pain resulting in lower extremity lacerations 6 months this activity for educational purposes only. Participants are D. Be amenable to Drug Enforcement Agency management regimens for an individual with prior, but continues to experience burning pain in expected to utilize their own expertise and judgment while audits. chronic pain and a history of substance abuse, his legs. He develops shooting pains that last for E. Must consider all potential side effects of any except: several minutes after a light touch anywhere on his engaged in the practice of medicine. The content of the medication. presentations is provided solely by presenters who have A. Methadone 10 mg orally four times daily. legs. His primary care physician has been 2. What is considered the “gold standard” for B. Buprenorphine 4 mg sublingually four times daily. prescribing hydrocodone with acetaminophen, and been selected for presentations because of recognized detecting possible substance abuse? C. Morphine sulfate immediate-release 10 mg is concerned that the patient has become addicted expertise in their field. A. A physician’s medical evaluation. orally every 4 h. to this medication. Which of the following is the B. Psychological tests such as the D. Lidoderm patch 5% topically once daily. most appropriate next step for the primary care DISCLOSURES Multidimensional Pain Inventory. E. Tramadol 50 mg orally four times daily. physician? Dr Gatchel has received research support and/or consultancy C. A patient’s past history of substance abuse. 3. Which of the following is the strongest risk factor A. Gradually taper off of fees from the Department of Defense, Endo Pharmaceuticals, D. A urine toxicology screen. for developing opioid abuse or dependence? hydrocodone/acetaminophen. the National Institutes of Health, PRIDE Research E. A functional capacity evaluation. A. Paternal grandfather has a history of B. Initiate methadone maintenance. Foundation, and West Coast Spine Restoration Center. 3. Which of the following is not a self-report measure alcoholism. C. Administer a naloxone challenge test. specifically developed for identifying potential B. Patient reports no improvement in pain after D. Refer the patient to a pain specialist. Dr Sullivan and Dr Manubay have no financial interests to medication abuse/misuse? escalating doses of pain medication 1 week E. Admit the patient to an addiction treatment disclose. Dr Comer serves as a consultant to Cephalon A. The Pain Medication Questionnaire. after the acute injury. program. Pharmaceuticals, King Pharmaceuticals, and Inflexxion. In B. The Screening Tool for Addiction Risk. C. Patient with a history of criminal activity 3. Which of the following is the primary purpose of a addition, she has received funding from Grunenthal GmbH C. The Screener and Opioid Assessment for including drug sales. medication agreement, or contract? and from Schering-Plough Corporation. Patients with Pain. D. Patient with an untreated anxiety disorder. A. Reduce physician legal liability. D. The Diagnostic and Statistical Manual of E. Patient comes from a low socioeconomic B. Outline the standards for patient discharge. Dr Weaver has served on the Speaker’s Bureau for PriCara Mental Disorders, 4th edition. background. C. Screen out high-risk patients for opioids. and the Advisory Board for Cephalon, Inc. Dr Schnoll has E. Opioid Risk Tool. 4. The following is/are reasonable methods to detect D. Facilitate physician-patient communication. received consultancy fees from Cephalon, Inc., Endo 4. What is the major reason why healthcare and manage aberrant drug behaviors, except: E. Highlight physician accountability. Pharmaceuticals, Javelin Pharmaceuticals, MEDA AB, and professionals receive “mixed messages” from A. Urine drug screening at each clinical visit. 4. A 40-year-old woman has been on extended- Purdue Pharma LP. federal agencies about over- or under-utilizing B. Use of screening instruments for aberrant release morphine for chronic pelvic pain for the opioid medications for pain? behaviors (i.e. Pain Assessment and past 8 months. She has demonstrated appropriate INSTRUCTIONS FOR OBTAINING CME CREDIT A. Because of the uncertainty of the drug’s Documentation Tool). adherence to all aspects of her pain management Participation in this activity should be completed in effectiveness. C. Calling family members and employers and plan. The results from her last urine drug screen B. Because of the cultural–legal atmosphere in the asking about any unusual behaviors. were negative for opioids, even though opioids approximately 2 h. To successfully complete this program US against narcotics. D. Use of treatment contracts that delineate had been detected on previous urine drug screens. and receive credit, participants must follow these steps: C. Because all physicians have a tendency to over- consequences of aberrant behaviors. Which of the following is the most appropriate 1. Read the learning objectives. prescribe such medications. E. All of the above are acceptable methods for next step? D. Because of the high costs of such medications. determining aberrant drug behaviors. A. Administer a naloxone challenge test. 2. Read the articles’ text and tables and review the figures. E. Because these drugs can be purchased 5. A 42-year-old Hispanic male has chronic low back B. Gradually taper off of extended-release 3. Visit the journal website “over the counter”. pain with no other medical problems and no morphine. C. Contact the testing laboratory for interpretation www.advancesinpainmanagement.com and follow 5. The most effective assessment approach for history of substance abuse. He falls in the category evaluating potential medication misuse in patients is: of the second step of the World Health of the result. the links to CME. A. A comprehensive assessment of all patients. Organization ladder for treatment of pain. Which D. Immediately discontinue prescribing controlled 4. Complete the registration information on the form B. A comprehensive assessment of all patients, of the following pain management regimens is substances to the patient. E. Notify the appropriate drug diversion included. along with the use of a specific “at-risk” best to manage his pain? questionnaire. A. Tylenol 1 g orally four times daily. authorities. 5. Read, complete, and submit answers to the self- C. There is no effective way. B. MS-Contin 30 mg orally twice daily and 5. A 24-year-old man has been treated for 6 months assessment questions. Participants must respond to D. The use of insurance companies to keep track morphine sulfate immediate-release 10 mg with extended-release oxycodone for chronic all program evaluation questions to receive a certificate of medication refill patterns. orally every 4 h, as needed. abdominal pain. Despite several increases in opioid by mail. E. A clinical interview with the patient. C. Vicodin 5/500 mg orally four times daily and dose by the practitioner, his pain remains severe. He 6. The most effective treatment approach for patients tylenol 500 mg orally every 6 h, as needed. has a history of major depression as a teenager, but Alternatively, complete the registration form, post-test who potentially require the use of opiate D. Oxycontin 40 mg orally twice daily. does not smoke or drink alcohol and has never used answer sheet, and evaluation form at the back of this medication is: E. Tramadol 50 mg orally four times daily and illicit drugs. Which of the following factors is the best journal and return to the address provided. A. The use of opiate medication is only needed. three lidoderm patches applied to skin once predictor of future aberrant medication-taking B. The use of opiates with other medications. daily. behavior for this patient? A. Age. A passing score of 70% or higher is required for issue of a C. An in-patient treatment program. 6. Which of the following disorders is frequently D. A comprehensive interdisciplinary pain found in patients abusing prescription opioids? B. Gender. statement of credit. management program. A. Depression. C. Severity of pain. E. There is currently no effective treatment. B. Panic disorder. D. Depression. C. Generalized anxiety disorder. E. Use of oxycodone. D. Antisocial personality disorder. 6. To which of the following effects of opioid E. All of the above. analgesics does tolerance develop most quickly? A. Analgesia. B. Respiratory depression. C. Euphoria. D. Miosis. E. Constipation. ¢
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Editor-in-Chief Ricardo A Cruciani, MD Contents Vice-Chairman and Director, Research Division, Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, Assistant Professor, Departments of Neurology and Anesthesiology, Albert Einstein College of Medicine, New York, Leading Articles NY, USA Methods for Monitoring Medication Use in Chronic Pain Patients Associate Editors Robert J Gatchel 54 Steven D Passik, PhD Associate Attending Psychologist, Memorial Sloan Kettering Cancer Center, Treatment Selection in Substance Abusers with Pain Associate Professor of Psychiatry, Weill College of Cornell Medical Center, New York, NY, USA Jeanne M Manubay, Sandra D Comer, Russell K Portenoy, MD and Maria A Sullivan 59 Chairman and Gerald J and Dorothy R Friedman Chair in Pain Medicine and Palliative Care, Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, Professor of Neurology and Anesthesiology, Albert Einstein Risk Assessment for Opioid Misuse College of Medicine, Chief Medical Officer, Continuum Hospice Care, New York, in Chronic Pain Treatment NY, USA Michael F Weaver and Sidney H Schnoll 68
Editors Case Study Lara Dhingra, PhD Patient Affected by Severe Cancer Pain Research Psychologist, Department of Pain Medicine and Palliative Care, Beth and Treated with Combined Strong Opioids Israel Medical Center, New York, NY, USA Elena Catala, Analia Azaro, and Marta Ferrandiz 76 Helena Knotkova, PhD Research Scientist, Research Division, Department of Pain Medicine and Palliative Care, Beth Medical Center, New York, NY, USA Clinical Reviews E Alessandra Strada PhD Neuropathic Pain 79 Attending Psychologist, Department of Pain and Palliative Care, Beth Israel Medical Center, New York, NY USA Chronic Pain 80 Editorial Advisory Board Breakthrough Pain 83 Miroslav Backonja, MD Professor of Neurology, Anesthesiology and Orthopedics & Rehabilitation, Director of Research and Education of the UW-Pain Treatment and Research Palliative Care 84 Center, Medical School, The University of Wisconsin, Madison, WI, USA Peggy Compton, PhD Animal Models 86 Associate Professor, School of Nursing, Acute Care Section, University of California Los Angeles, Los Angeles, CA, USA Edward C Covington, PhD Miscellaneous 88 Director, Chronic Pain Rehabilitation, Cleveland Clinic Foundation, Cleveland, OH, USA Meeting Report Robert Dworkin, PhD Highlights from the American Pain Foundation’s Professor of Anesthesiology, Neurology, Oncology, and Psychiatry, Director, Anesthesiology Clinical Research Center, University of Rochester School of Roundtable. Provider Prescribing Patterns and Medicine and Dentistry, Rochester, NY, USA Perceptions: Identifying Solutions to Build Doug Gourlay, MD Consensus on Opioid Use in Pain Management Medical Consultant, Pain and Chemical Dependency Division, The Wasser Pain Micke A Brown and Amanda Crowe 92 Management Centre, Mount Sinai Hospital, The Centre for Addiction and Mental Health, Toronto, ON, Canada Martin Grabois, MD Forthcoming International Events 96 Professor and Chairman, Physical Medicine andRehabilitation, Professor, Anesthesiology, Baylor College of Medicine, Professor, Physical Medicine and Rehabilitation, University of Texas Health Science Center-Houston, Houston, TX, USA Francis Keefe, PhD Professor, Department of Psychiatry and Behavioral Sciences, Director, Pain Prevention and Treatment Research Program, Professor of Medicine, Professor in Anesthesiology, Duke University Medical Center, Durham, NC, USA Jianren Mao, MD Associate Professor, Director, MGH Center for Translational Pain Research, Division of Pain Medicine, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Judith A Paice, PhD Director, Cancer Pain Program, Division of Hematology-Oncology, Northwestern University; Feinberg School of Medicine, Chicago, IL, USA Neal Slatkin, PhD Director, Department of Supportive Care, Pain and Palliative Medicine, Professor, Division of Medicine, Departments of Supportive Care, Pain and Palliative Medicine and Neurology, City of Hope National Medical Center, Duarte, CA, USA RT379_4_REM_Pain_Man_2_2_07.qxd 10/21/08 2:24 PM Page 54
Methods for Monitoring Medication Use in Chronic Pain Patients
Robert J Gatchel, PhD, ABPP University of Texas, Arlington, TX, USA
In this article, the best methods for assessing chronic pain patients who are potentially at risk of misuse or abuse of pain- reduction medications are highlighted. The author recommends that comprehensive biopsychosocial assessments of such LEADING ARTICLE patients should be conducted using instruments specifically developed for evaluating the potential for abuse/misuse. The Pain Medication Questionnaire is discussed as an example of one such tool. The advantages of this comprehensive assessment approach, which has been shown to be the most heuristic perspective for the evaluation and treatment of chronic pain, are reviewed. Finally, an algorithm for the ongoing evaluation of patients undergoing opioid treatment is presented. Adv Pain Manage 2008;2(2):54–58
As Katz and Barkin have recently reviewed, although a • Justification for the medical use of the drug. variety of pharmacological treatments are currently available • Assessment of patients for possible current addiction for patients suffering from chronic and persistent pain, such prior to dispensing a prescription. pain is often inadequately managed [1]. This results in • The need for accurate records of prescribing practices chronic pain remaining a substantial problem for patients in each patient’s chart, which are subject to a Drug and for society as a whole. Reasons for inadequate Enforcement Agency (DEA) audit at any time. pharmacological treatment include: Medical licenses have been revoked for failure to adhere • The need for multiple doses of opiates for continuous to the above regulations. Consequently, many physicians pain relief, with resultant inconvenience/time-compliance have developed “opiophobia” – a term coined by the issues that may prevent patients from achieving pharmacologist John Morgan in 1986. Opiophobia is adequate pain relief. defined as a fear of opiate prescribing, with an inherent • Side effects, such as gastrointestinal, cardiovascular, and prejudice against these types of drugs regardless of their organ toxicity. appropriate clinical utility. • The fear of abuse or addiction. Thus, clinicians today are faced with a major conundrum. Despite the known benefits of opioid therapy and the growing Added to these reasons, and of particular concern for number of such medications available for patients with chronic many healthcare professionals, is the fear of being perceived pain [5,6], many physicians are hesitant to prescribe them as complicit in increasing the rates of abuse or addiction [2]. because they are either opiophobic or because they do not Misuse/abuse of controlled substances, such as opiates, is have an adequate understanding of the risks of potential escalating at a rate commensurate with the number of misuse and abuse. As Turk et al. have reviewed, this has prescriptions in the US [3,4]. In an effort to control this stimulated the search for strategies with which to identify problem, prescribing physicians are legally required to patients who are potentially at risk of misuse or abuse [7]. It consider a number of issues prior to dispensing such has also been noted that a subset of patients, estimated to be prescriptions including: in the range of 2.8–62.2% (depending on the study and patient group evaluated), have such potential [4,8–10]. Of Address for correspondence: Robert J Gatchel, Nancy P & John G course, for these patients greater vigilance is required. Penson Endowed Professor of Clinical Health Psychology, and Therefore, the following guidelines should be followed: Chairman, Department of Psychology, College of Science, The University of Texas at Arlington, 501 S Nedderman Drive Ste 313, • A single physician should take primary responsibility for Arlington, TX 76019–0528, USA. Email: [email protected] the opioid medication.
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METHODS FOR MONITORING MEDICATION USE IN CHRONIC PAIN PATIENTS
• The patient must be evaluated in person when the weaknesses. In general, assessment data are greatly needed prescription is to be refilled and refills should not be by healthcare professionals in order to more effectively prescribed over the telephone. evaluate the potential benefits and risks of prescribing long- • A clear medication agreement is needed to delineate which term opioid treatment. An algorithm for the ongoing emergency situations justify early refill of a prescription. evaluation of opioid treatment is presented in Figure 1. • Early refills should be minimal and carefully monitored, using only one pharmacy. Monitoring the potential for medication abuse/misuse The terms “abuse” and “misuse” are used repeatedly Recent reviews by Bernstein et al. [2], Schatman [16], and throughout this article. Abuse is a diagnostic category of the Turk et al. [7] have addressed the best methods for assessing Diagnostic and Statistical Manual of Mental Disorders 4th patients potentially at risk of misuse/abuse of pain-reduction edition that refers to a maladaptive pattern of psychoactive medications. The “gold standard” for detecting drug use (be substance usage outside of sociocultural conventions or it substance abuse, misuse, or simply recreational use) is urine when there are no longer positive therapeutic indications. As toxicology screening, which many clinicians suggest should be noted by Polatin and Gajraj, “by definition, all use of illicit routinely used for all patients who receive chronic opioids drugs is abuse, as is use of drugs not according to a [17]. However, even the results of such screens need to be physician’s orders” [11]. The term misuse reflects the latter interpreted with some caution for the following reasons: part of the above quotation – i.e. use of the medication in other than the prescribed manner. • Lack of an initially positive urine screen cannot be In light of the above issues, an important goal for those mindlessly used as a predictor of all future drug advocating the use of opioid medication is the development of abuse/misuse behavior in all patients. a reliable method of evaluating the patient risk associated with • Even patients with an initially negative screen may potential abuse/misuse. This is especially important for patients subsequently display behaviors indicative of substance with chronic pain, among whom urine toxicology screening abuse/misuse [18]. results indicate that abuse/misuse is a significant problem in • An initial positive urine toxicology screen may not those treated with opioids (range 27.2–42.0%) [7]. Ballantyne accurately predict future abuse/misuse problems [18]. and Mao have argued that the optimally effective use of opioids must include an evaluation of the potential for abuse in One important starting point for avoiding the potential all patients being considered for such therapy [12]. for medication abuse is to address the issue at the beginning At the outset, it should also be kept in mind that the use of any intervention. A medication agreement in which it is of opioid therapy (simple monotherapy) is not as effective as clearly stated that it is the responsibility of the patient not to by a more comprehensive, interdisciplinary pain management misuse any drugs, and having the patient sign an agreement program [13]. As previously elucidated by Gatchel, as well as to that effect, can help to achieve this. It should also be by Turk and Monarch, the biopsychosocial model has become noted that the term “agreement” must be used rather than the most heuristic approach to truly understanding and “contract”, because the latter implies a legal document treating chronic pain [14,15]. In this model, a physical (which it is not) [14]. Moreover, if the patient has a number syndrome, such as chronic pain, is viewed as the result of an of medications prescribed over the years by many different intricate and dynamic interaction among biological, physicians (e.g. benzodiazepines for anxiety/stress, a muscle psychological, and social factors. Thus, individuals tend to relaxant, a medication for sleep, as well as multiple narcotic express variability in their pain experiences due to the range medications for pain), then a detoxification program (either of interaction between these factors that modulates the inpatient or outpatient) may need to be arranged so that the interpretation of symptoms. Therefore, the biopsychosocial patient–physician team can start a new opioid intervention model uses physical, psychological, social, cognitive, affective, strategy with a “clean slate.” Unfortunately, there are no and behavioral measures – along with their interactions – to standard empirical guidelines for making this decision, and it best assess the individual’s unique pain condition. Factors such has been generally left to the clinician’s preference/ as a patient’s positive and negative coping skills, current level experience with such issues. of stress, social support, and negative cognitions (such as catastrophizing) must be taken into account in order to obtain Measures for monitoring potential a complete picture of the patient’s strengths and weaknesses. medication abuse/misuse A treatment program can then be tailored to each patient so Identifying other measures that can be used to flag those as to further maximize his or her strengths and help eliminate patients who are potentially at risk of future medication
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ROBERT J GATCHEL
Figure 1. Proposed algorithm for the ongoing evaluation of opioid treatment.
Strong indication of current medication abuse/misuse1
Yes No
Detox program2 • Comprehensive biopsychosocial evaluation • PMQ • Medication use agreement • Baseline urine toxicology screen • Diligent written documentation in patient chart for each patient contact (e.g. in person, telephone, email, pharmacy calls)
Any “red flags” (e.g. high PMQ score, positive urine screen)?
Yes No
• Random urine screens • Greatest vigilance needed • Re-administer PMQ • Refills only in person • Continue diligent documentation • Constant evaluation of effectiveness of opioid therapy
Treatment exit strategy
1For example, aberrant behavior such as forging prescriptions, frequently losing prescriptions, stealing or borrowing drugs, or a history of legal problems [7,29]. 2It should be noted that there are no standard empirical guidelines for making the decision for the need of a detoxification program, and it has generally been left to the clinician’s preference/experience with such issues. Many factors need to be considered and, when in doubt, consultation with a pain management/addiction specialist should be considered. PMQ: Pain Medication Questionnaire.
abuse/misuse, enabling physicians to take special • Drop-out rate was 2.3-times higher than in the precautions in their treatment, remains an unresolved issue. low-PMQ-score patients. In response to this, a number of instruments have been • Diminished biopsychosocial functioning. developed. Table 1 provides a list of such tools. • At 6 months after treatment discharge, patients who Of the listed instruments, the Pain Medication completed the program showed a significant decrease in Questionnaire (PMQ) has, in particular, received a great deal PMQ scores over time. of interest as a result of the initial studies by Adams et al. [19] and Holmes et al. [20]. Therefore, for the purpose of brevity, There are also a number of other important benefits the main focus in the present article is this questionnaire. The associated with the PMQ. For example, it has been shown PMQ was designed to assess the risk of medication misuse in to be psychometrically sound. The two core psychometric chronic pain patients. Adams et al. initially found a positive properties of any test are reliability and validity. Reliability relationship between higher PMQ scores and concurrent refers to the reproducibility of a test from one administration measures of substance abuse, psychopathology, and to the next. One would expect that if a test is administered physical/life-functioning. Holmes et al. subsequently replicated at two different points in time, with no major intervening these results, and in addition found the following circumstances possibly affecting the test, then the test–retest characteristics in high-PMQ-score patients: reliability should be high. The PMQ has been shown to have significant reliability (e.g. test–retest reliability coefficient of • History of substance abuse problem was 2.6-times 0.86; internal consistency, Cronbach’s alpha of 0.73). higher than in the low-PMQ-score patients. Validity refers to the appropriateness and usefulness of a • Early refills of prescription medications were requested particular test or measurement in making an inference about 3.2-times more than in the low-PMQ-score patients. an individual’s behavior (in this case, a patient’s potential for
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Table 1. Methods developed to identify potential medication misuse. Tools Description Interviews and observations Aberrant behaviors identified by clinicians [21,22] Such behaviors include forging prescriptions, stealing or borrowing drugs, frequently losing prescriptions, and resisting changes to medication despite adverse side effects Checklist of risk behaviors [9] This checklist consists of the following items: patient’s strong focus on opioids during treatment, a pattern of early refills or escalating medication use in the absence of positive clinical change, multiple telephone calls or visits related to requests for opioid prescriptions, a pattern of prescription “problems” (e.g. lost or stolen medication), and access to supplemental sources of opioids PDUQ [23] The PDUQ follows a structured interview format, with patients being questioned about their pain condition, opioid use pattern, family history of pain and substance abuse, social and family factors, history of substance abuse, and psychiatric history. One limitation of the PDUQ is that it has to be administered by a trained clinician
Self-report questionnaires STAR [24] The STAR consists of questions about the following details: employment status; history of, and current presence of, emotional problems, drug/alcohol/cigarette use, and treatment; family history of illicit drugs for pain treatment; and history of childhood physical or verbal abuse SISAP [25] The SISAP was designed to work best as an adjunct instrument, when the patient is well known to the clinician and the judgment of the clinician plays an important role. It was developed and validated using data acquired from a population-based telephone National Alcohol and Drug Use Survey conducted by Statistics Canada and Health and Welfare Canada in 1989. SISAP consists of questions about the use of prescription medication, over-the-counter medication, illicit drugs, and alcohol. SOAPP [26] The SOAPP includes questions about substance abuse, medication use problems, smoking behavior, psychosocial problems, and legal problems. Questions are based on items provided by an expert panel whose role is to identify and rate risk factors for potential problems associated with opioid use by chronic pain patients ORT [27] The ORT includes questions in the following areas: family and personal history of substance abuse, psychiatric diagnoses, history of sexual abuse, and age. The questions are weighted and then summed together to yield a level of risk COMM [28] The major goal of the COMM, in contrast to the other measures described, is to monitor the misuse of medications in patients who have been prescribed opioids over an extended period of time. An expert panel of pain and addiction specialists as well as primary care providers identify a specific list of aberrant and drug-related behaviors of chronic pain patients who are already prescribed and taking opioids. PMQ [19] The PMQ is described at length in the body of this article
COMM: Current Opioid Misuse Measure; ORT: Opioid Risk Tool; PDUQ: Prescription Drug Use Questionnaire; PMQ: Pain Medicine Questionnaire; SISAP: Screening Instrument for Substance Abuse Potential; SOAPP: Screener and Opioid Assessment for Patients with Pain; STAR: Screening Tool for Addiction Risk.
medication misuse). The PMQ has been shown to have requiring a third-grade reading level). Other advantages of good validity (e.g. concurrent validity with indices of using the PMQ include the following: substance use/abuse, p<0.01; known opioid abuse p<0.05). In addition, the PMQ is a brief 26-item self-report • Demonstration of due diligence of the clinician in instrument that can be filled out easily by patients (only monitoring prescription use for any potential DEA audit.
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• Increased quality assurance in terms of the treatment References 1. Katz WA, Barkin RL. Dilemmas in chronic/persistent pain management. Am J Ther program, as well as helping to tailor the program to the 2008;15:256–64. specific needs of patients. 2. Bernstein D, Stowell AW, Haggard R et al. Complex interplay of participants in opioid • Production of better overall outcomes of the treatment therapy. Practical Pain Management 2007;7:10–36. 3. Reid MC, Engles-Horton LL, Weber MB et al. Use of opioid medications for chronic program – this is good “public relations” for use with noncancer pain syndromes in primary care. J Gen Intern Med 2002;17:173–9. 4. Soderstrom CA, Dischinger PC, Kerns TJ et al. Epidemic increases in cocaine and opiate use insurance carriers. by trauma center patients: documentation with a large clinical toxicology database. • High sensitivity of 0.90. J Trauma 2001;51:557–64. 5. Joranson DE, Carrow GM, Ryan KM et al. Pain management and prescription monitoring. J Pain Symptom Manage 2002;23:231–8. Summary and conclusions 6. Joranson DE, Gilson AM, Dahl JL et al. Pain management, controlled substances, and state medical board policy: a decade of change. J Pain Symptom Manage 2002;23:138–47. Opioids and other pain-reducing medications (such as 7. Turk DC, Swanson DC, Gatchel RJ. Predicting opioid misuse by chronic pain patients: a benzodiazepines, antidepressants, and neuroleptics) have a systematic review and literature synthesis. Clin J Pain 2008;24:497–508. 8. Martell BA, O’Connor PG, Kerns RD et al. Opioid treatment for chronic back pain: a very important role in chronic pain management. However, systematic review and meta-analysis of their prevalence, efficacy and association with addiction. Ann Intern Med 2007;146:116–27. because of the cultural–legal atmosphere in the US 9. Chabal C, Erjavec MK, Jacobson L et al. Prescription opiate abuse in chronic pain patients: surrounding narcotics, healthcare professionals receive clinical criteria, incidence and predictors. Clin J Pain 1997;13:150–5. 10. Gilson AM, Ryan KM, Joranson DE et al. A reassessment of trends in the medical use and mixed messages from federal agencies about over- and abuse of opioid analgesics and implications for diversion control: 1997–2002. J Pain under-utilizing such medications. Physicians are not Symptom Manage 2004;28:176–88. 11. Polatin PB, Gajraj NM. Integration of pharmacotherapy with psychological treatment of blameless in this area, as many have been cavalier in the chronic pain. In: Turk DC, Gatchel RJ, editors. Psychological Approaches to Pain Management: A Practitioner’s Handbook. New York, NY: Guilford Press, 2002:276–96. past regarding prescription behaviors. With this universal 12. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med 2003;349:1943–53. precaution in mind, healthcare providers are required to 13. Gatchel RJ, Okifuji A. Evidence-based scientific data documenting the treatment- and cost-effectiveness of comprehensive pain programs for chronic nonmalignant pain. J Pain document the steps they have taken to minimize the risk of 2006;7:779–93. potential abuse/misuse of opioid medications that they 14. Gatchel RJ. Clinical Essentials of Pain Management. Washington, DC: American Psychological Association, 2005. prescribe. An at-risk screening instrument, such as the PMQ, 15. Turk DC, Monarch ES. Biopsychosocial perspective on chronic pain. In: Turk DC, Gatchel should be used together with data gleaned from the RJ, editors. Psychological Approaches to Pain Management: A Practitioner’s Handbook. 2nd editon. New York, NY: Guilford Press, 2002:3–29. remaining biopsychosocial assessment material in order to 16. Schatman ME. Identifying abusers prior to initiating chronic opioid therapy. Practical Pain obtain the best estimate of risk potential. Management 2008;8:54–61. 17. Scheider J, Miller A. Urine drug tests in a private chronic pain practice. Practical Pain Finally, another important aspect in the treatment of Management 2008;8:62–7. 18. Katz NP, Sherburne S, Beach M et al. Behavioral monitoring and urine toxicology testing in chronic pain is that the use of opioid therapy should be only patients receiving long-term opioid therapy. Anesth Analg 2003;97:1097–102. one aspect of a more comprehensive biopsychosocial 19. Adams LL, Gatchel RJ, Robinson RC et al. Development of a self-report screening instrument for assessing potential opioid medication misuse in chronic pain patients. J Pain evaluation in the form of an interdisciplinary pain Symptom Manage 2004;27:440–59. management program. Such a program should include 20. Holmes CP, Gatchel RJ, Adams LL et al. An opioid screening instrument: long-term evaluation of the utility of the Pain Medication Questionnaire. Pain Pract 2006;6:74–88. pharmacotherapy, behavioral medicine treatment, physical 21. Portenoy RK. Chronic opioid therapy in nonmalignant pain. J Pain Symptom Manage therapy, and occupational therapy, all coordinated by a 1990;5:S46–62. 22. Portenoy RK, Foley KM, Inturrisi CE. The nature of opioid responsiveness and its physician–nurse team. Furthermore, an appropriate “exit implications for neuropathic pain: new hypotheses derived from studies of opioid infusions. Pain 1990;43:273–86. strategy” needs to be in place in order to discontinue the 23. Compton P, Darakjian MA, Miotto K. Screening for addiction in patients with chronic pain use of opioids when a patient is not attaining appropriate and “problematic” substance use: evaluation of a pilot assessment tool. J Pain Symptom Manage 1998;16:355–63. goals of a comprehensive treatment program, or if 24. Friedman R, Li V, Mehrotra D. Treating pain patients at risk: evaluation of a screening tool problematic behaviors develop and persist over time. in opioid-treated pain patients with and without addiction. Pain Med 2003;4:182–5. 25. Coambs RB, Jarry JL, Santhiapillai AC et al. The SISAP: a new screening instrument for identifying potential opioid abusers in the management of chronic malignant pain within general medical practice. Pain Res Manag 1996;1:155–62. Acknowledgments 26. Butler SF, Budman SH, Fernandez K et al. Validation of a screener and opioid assessment This research was supported in parts by grants No. 5R01 MH46452 and measure for patients with chronic pain. Pain 2004;112:65–75. 27. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: 1K05 MH71892 from the US National Institutes of Health and grant preliminary validation of the opioid risk tool. Pain Med 2005;6:432–42. No. DAMD17-03-1-0055 from the US Department of Defense. 28. Butler SF, Simon HB, Fernandez KC et al. Development and validation of the current opioid misuse measure. Pain 2007;130:144–6. 29. Portenoy RK. Opioid therapy for chronic nonmalignant pain: a review of the critical issues. Disclosures J Pain Symptom Manage 1996;11:203–17. Dr Gatchel has received research support and/or consultancy fees from the Department of Defense, Endo pharmaceuticles, the National Institutes of Health, PRIDE Research Foundation, and West Coast Spine Restoration Center.
58 ADVANCES IN PAIN MANAGEMENT Vol 2 No 2 2008 LEADING ARTICLE , es 59 ermine (2):59–67. 2 ; Adv Pain Manage 2008 Vol 2 No 2 2008 Vol The presence of psychiatric illness, either pre-dating the of psychiatric illness, either pre-dating The presence by of social support should be explored The degree patients, with observed prevalence rates of 19–41% [6–8]. rates of patients, with observed prevalence study of patients with chronic prospective large, In a recent individuals with panic disorder, disabling spinal disorders, and dependent personality antisocial personality disorder, [9]. non-completers likely to be program more were disorder associated with were work outcomes In addition, poorer dependence. particularly opioid Axis I psychiatric disorders, it, can make it pain condition or arising as a consequence of to function or be able to live with for some patients difficult include a an initial evaluation should pain. Therefore, chronic or In addition, any personal psychiatric history. thorough a vulnerability family history of substance abuse can predict opioid chronic to addiction, especially in the context of therapy [10,11]. inquiring about family and friends or significant others. Information about education, work, housing, access to or crime will yield a services, and legal problems healthcare level of accurate understanding of a patient’s more cultural norms and spiritual beliefs functioning. Furthermore, influence how a patient experiences pain and may strongly a will reveal illness. Investigating these areas perceives and vulnerabilities, and help to identify strengths patient’s stress. interventions that may reduce appropriate ANAGEMENT M AIN P DVANCES IN A Among primary care patients with chronic low back pain, low patients with chronic Among primary care the lifetime and current prevalence of substance use of substance prevalence the lifetime and current [3]. found to be 54% and 23%, respectively were disorders with substance abuse, other comorbid psychiatric Together pain patients are experienced by chronic frequently disorders [4]. Panic disorder and anxiety disorders major depression found to be most with agoraphobia is the anxiety disorder opioid use [5]. to non-medical prescription related strongly pain also common among chronic are Personality disorders The experience of pain is multifaceted and includes physical The experience of pain is multifaceted and includes of spirituality and psychological factors, as well as the context of a disease and socio-cultural values. Pain is usually the result by prior experiences of pain, personality but is affected process and support, motivation, factors, coping strategies, perceived assessing these factors, clinicians may [1,2]. By self-efficacy of the patient’s appreciation comprehensive develop a more the best ways subjective pain experience, and can then identify quality of life and help to maximize to individualize treatment for developing a clinical guideline (QoL). This article provides pain in patients plan to manage chronic treatment an effective with comorbid substance abuse. and addiction risk provide structure and help to facilitate an understanding of pain and methods of coping. Continual of pain and methods of coping. structure and help to facilitate an understanding and addiction risk provide at the first the course of treatment. Delineating rules can then guide the clinician throughout assessment of these factors agreement enables clinicians to identify problematic behaviors and address encounter with a patient by using a treatment risk categories for addiction liability will make it easier for a clinician to det Stratifying patients into these accordingly. the need for outside referrals. Identification and treatment of psychiatric issu individualized treatment strategies, including may also facilitate pain management. This article will help guide clinicians in and an understanding of personality disorders to structure the assessment and treatment of pain on an ongoing basis. understanding the pain experience, and help substance abusers are discussed. Recommendations for treatment selection in The treatment of chronic pain in substance abusers poses a clinical challenge in light of the broader availability, increased challenge in light of the broader availability, pain in substance abusers poses a clinical The treatment of chronic and factors that contribute to the pain experience of prescription opioids. By reviewing the various abuse, and diversion be managed chronic pain in substance abusers may of mood disorders or aberrant behaviors, assessing the presence be routinely used. testing, and psychiatric assessments should agreements, urine toxicology Treatment successfully. strategies functioning, quality of life, pain beliefs, coping for assessing pain, emotional and physical Additional instruments Jeanne M Manubay, MD, Sandra D Comer, PhD, and Maria A Sullivan, MD, PhD PhD, Sandra D Comer, MD, Jeanne M Manubay, USA NY, Institute, New York, State Psychiatric and The New York Columbia University Treatment Selection in Selection Treatment with Pain Abusers Substance Address for correspondence: Maria A Sullivan, Columbia University and for correspondence: Address State Psychiatric Institute, 1051 Riverside Drive, Unit 120, The New York NY 10032, USA. 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Assessment of pain the Mini-International Neuropsychiatric Interview (for When assessing pain, it is important to select clinical Diagnostic and Statistical Manual of Mental Disorders, 4th instruments that can evaluate various dimensions of pain to edition [DSM-IV] and International Classification of Diseases, help guide treatment. In this section, clinical guidelines for 10th Revision psychiatric disorders), the Patient Health understanding pain using a biopsychosocial approach are Questionnaire-9 (based on DSM-IV criteria for major discussed. For each category, several available assessment depression), the Beck Depression Inventory, and the Hamilton measures are described. This review of pain assessment Depression Scale [20–23]. scales is intended to help clinicians determine which tools are most appropriate for their patient population. In many Beliefs, cognitions, and coping strategies cases, employing one measure from each section below will Knowledge of a patient’s beliefs and cognitions can aid in enable a comprehensive clinical assessment of the patient’s understanding how he or she copes with pain. The Coping overall pain experience. Strategies Questionnaire Catastrophizing Scale assesses the frequency of intense negative cognitions in response to pain The pain experience (e.g. “I worry all the time about whether it will end”) [24]. Average pain intensity is often measured on an 11-point The Survey of Pain Attitudes Scale assesses the following (i.e. 0–10) numerical rating scale, a visual analogue scale, or a domains of pain beliefs [25]: verbal rating scale (0=no pain, 10=worst pain you can imagine) [12]. Each of these methods is helpful in monitoring • Control (over pain). changes in pain intensity over time, usually the last 24 h or the • Disability (that one is disabled by pain). last week of the clinical assessment period. The Short-Form • Harm (that pain is a signal of bodily damage). McGill Pain Questionnaire measures pain quality through 15 • Emotion (that emotions influence pain). specific sensory and affective pain descriptors (e.g. throbbing, • Medical cure. shooting, tiring/exhausting, sickening, cruel/punishing) [13]. • Solicitude (that others should be solicitous). • Medication (appropriateness of medications). Physical functioning Several disease-specific measures of physical functioning The Chronic Pain Coping Inventory evaluates the have been developed, such as the Oswestry Disability frequency with which chronic pain patients use a variety of Questionnaire and the Roland and Morris Back Pain coping strategies (e.g. resting, asking for assistance, exercise, Disability Scale for assessing the disabling effects of lumbar and seeking social support) in response to pain [26]. This spinal disorders [14,15]. Both the Multi-Dimensional Pain instrument can guide clinicians in teaching and monitoring Inventory Interference Scale and the Brief Pain Inventory of behavioral strategies for coping with pain. Social support address the cognitive and behavioral aspects of pain, can be measured using the Multidimensional Scale of including interference with daily life, mood, sense of control, Perceived Social Support (MSPSS), which has three subscales and impact on activities [16,17]. The 36-item Short-Form – family, friends, and significant other [27]. Health Survey, the most commonly used measure of health- related QoL, consists of both mental and physical Outcome and satisfaction with treatment component scales [18]. A short version of the World Health During the treatment of chronic pain, it is essential to Organization (WHO) QoL instrument WHOQOL-BREF was monitor a patient’s perception of pain relief. The Impression developed to be an international, cross-culturally compatible of Overall Status scale is rated by both patient and clinician QoL assessment tool [19]. It measures domains of to determine if pain is improving or worsening [28]. physical health, psychological health, social relationships, Another measure to help guide clinicians with their and environment. therapeutic decisions is the Pain Assessment and Documentation Tool (PADT) [29]. This tool incorporates an Emotional functioning assessment of the “4 As”: analgesia, activity, adverse Psychological distress will influence one’s experience of effects, and aberrant behavior. It is important to identify chronic pain. Symptoms of depression and anxiety may aberrant behaviors as they may signal potential misuse of either pre-date the onset of pain conditions, or be a opioids. Several investigators have sought to identify consequence of chronic pain. Evaluating patients for aberrant behaviors that may reliably indicate a substance underlying psychiatric disorders may help guide treatment. abuse disorder [30,31]. Such behaviors are listed in Table 2, Several structured diagnostic instruments (listed in Table 1) and range from failing to comply with a prescribed regimen are available to assess psychiatric disorders. Among these are to clearly illegal behaviors.
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Table 1. Selected physical and mental health diagnoses in chronic opioid, acute opioid, and non-opioid treatment groups in the state of Missouri, USA, in 2004.
Mode of No. of Estimated time Areas of assessment Advantages/disadvantages rating items to complete Pain experience
Pain intensity scale Self 1 Average pain intensity <1 min Easy to understand. R&V (NRS) [12]
Pain intensity scale Self 1 Average pain intensity <1 min May be too abstract for some. (VAS) [12] R&V
Pain intensity scale Self 1 Average pain intensity <1 min Easier for patients with cognitive (VRS) [12] impairment. R&V
SF-MPQ [13] Self 15 A total of 15 specific sensory 5 min May be capable of discriminating and affective pain descriptors among different pain syndromes. R&V Physical functioning
WHYMPI [16] Self 61 Family support and interaction, 15 min Applicable across a wide range of pain intensity, activity levels pain types, locations, and etiologies. Sensitive to psychosocial functioning. Does not assess sleep. R&V
BPI [17] Self 32 Pain interference (with general 10–15 min Can be used in diverse chronic pain activity, mood, walking ability, conditions. Assesses the impact of sleep, enjoyment of life) pain on sleep. R&V across cultures and languages
ODQ [14] Self 10 Disability effects of lumbar 5–10 min “Gold standard” of low back spinal disorders functional outcome tools. R&V Quality of life
SF-36 [18] Self 36 Mental component scale and 10 min Allows comparisons among physical component scale different medical disorders, and indicate a patient’s overall sense views both pre- and post- of mental and physical wellbeing treatment. R&V
WHOQOL-BREF Self 26 Perceptions of physical and 10 min An international, cross-culturally [19] psychological health, social compatible quality-of-life relationships and environment instrument. Depression can be a in the context of culture confound. R&V and values
Emotional functioning
PHQ [21] Self 9 Depressive symptoms and 2–3 min Brief. Can diagnose and indicate functional impairment severity of depression. Based on the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. R&V
BDI [22] Self 21 Depressive symptoms 10 min Requires a sixth-grade reading level. Helpful in distinguishing severity of depression (dysthymia vs. MDD). R&V
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Table 1 (cont.). Selected physical and mental health diagnoses in chronic opioid, acute opioid, and non-opioid treatment groups in the state of Missouri, USA, in 2004.
Mode of No. of Estimated time Areas of assessment Advantages/disadvantages rating items to complete Emotional functioning
HAMD [23] Clinician 21 Depressive symptoms 10 min One of the most commonly used scales for rating depression in medical research. Sensitive to somatic symptoms (possible confound). R&V
MINI [20] Clinician Diagnostic for 15 min Short but accurate, structured, 17 psychiatric disorders psychiatric interview. R&V Beliefs, cognitions, coping strategies
CSQ-CAT [24] Self 6 Frequency of catastrophizing 5 min Useful in determining patient’s cognitions in response to pain self-efficacy. Excellent internal consistency and good validity SOPA [25] Self 57 Pain beliefs: control, disability, 10 min Measures attitudes and ways emotion, medical cure, patients manage pain. Easily solicitude, medication administered and scored. R&V
CPCI [26] Self 70 Frequency of using a variety of 10 min Guides clinicians in teaching coping strategies in response to behavioral strategies for coping pain (guarding, resting, asking with pain. Measures change in for assistance, relaxation, task coping strategies over time or with persistence, exercise/strength, treatment. R&V seeking social support, coping self-statements and pacing)
MSPSS [27] Self 12 Perceptions of social support 5 min Assesses role of social environment available from family, friends, in adjustment to pain. R&V and significant others Outcome and satisfaction of treatment
Impression of overall Self, 1 Perception of pain relief 1 min Can compare patient and clinician status scale [28] clinician impression of overall status across time to guide treatment
PADT [29] Clinician 14 The 4As: analgesia, activities 5 min Assesses pain outcomes to of daily living, adverse optimize therapy. Identifies events, potential aberrant aberrant behaviors drug-related behavior
Screening for addiction risk
PMQ [35] Self 26 Concurrent substance abuse, 10 min Identifies patients in need of more psychopathology and in-depth assessment of risk for physical/life-functioning opioid misuse
ORT [32] Self 5 Personal and family history of 1–2 min Measures level of risk (low, medium, substance abuse, history of high) for aberrant behaviors preadolescent sexual abuse, psychological disorders
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Table 1 (cont.). Selected physical and mental health diagnoses in chronic opioid, acute opioid, and non-opioid treatment groups in the state of Missouri, USA, in 2004.
Mode of No. of Estimated time Areas of assessment Advantages/disadvantages rating items to complete Screening for addiction risk
SOAPP [33] Self 24 Substance abuse history, 10 min Helps to determine potential risk of doctor–patient relationship, abuse through a broad assessment antisocial behavior, medication- of patient’s behavior. R&V related behaviors, personal care, lifestyle, need for medication, psychiatric and psychosocial issues
PDUQ [34] Clinician 42 Pain condition, opioid-use 20 min Screens for addictive behaviors in patterns, social and family chronic pain patients, but takes factors, family history of pain longer to administer and substance abuse, psychiatric history
COMM [36] Self 17 Frequency of aberrant 5–10 min Assesses ongoing medication cognitions and behaviors in the misuse in patients already on last 30 days of clinical chronic opioid therapy assessment
BDI: Beck Depression Inventory; BPI: Brief Pain Inventory; COMM: Current Opioid Misuse Measure; CPCI: Chronic Pain Coping Inventory; CSQ-CAT: Coping Strategies Questionnaire Catastrophizing scale; HAMD: Hamilton Depression scale; MDD: major depressive disorder; MINI: Mini-International Neuropsychiatric Interview; MSPSS: Multidimensional Scale of Perceived Social Support; NRS: Numerical Rating Scale; ODQ: Oswestry Disability Questionnaire; ORT: Opioid Risk Tool; PADT: Pain Assessment and Documentation Tool; PDUQ: Prescription Drug Use Questionnaire; PHQ: Patient Health Questionnaire; PMQ: Pain Medicine Questionnaire; R&V: reliable and valid; SF-36: Short Form-36 mental health survey; SF-MPQ: Short-Form McGill Pain Questionnaire; SOAPP: Screener and Opioid Assessment for Patients with Pain; SOPA: Survey of Pain Attitudes scale; VAS: Visual Analogue Scale; VRS: Verbal Rating Scale; WHOQOL-BREF: World Health Organization Quality of Life Instrument; WHYMPI: West Haven–Yale Multidimensional Pain Inventory interference scale.
Structured measures for risk assessment Table 2. Aberrant behaviors that may indicate a substance Screening instruments for addiction that are specific for abuse disorder [30,31]. opioid-dependent patients include Opioid Risk Tool (ORT) • Selling prescription drugs [32], Screener and Opioid Assessment for Patients with Pain (SOAPP) [33], Prescription Drug Use Questionnaire (PDUQ) • Forging prescriptions [34], and Pain Medicine Questionnaire (PMQ) [35]. • Stealing drugs The ORT has a high degree of sensitivity and specificity for determining which individuals are at risk for opioid- • Injecting oral formulations related, aberrant behaviors [32]. This tool measures risk • Obtaining prescription drugs from non-medical sources factors associated with substance abuse: personal or family history of substance abuse, age, history of preadolescent • Concurrently abusing alcohol or other illicit drugs sexual abuse, and certain psychological disorders. • Escalating doses on multiple occasions or otherwise The SOAPP was developed to determine the potential failing to comply with the prescribed regimen despite risk of abuse when prescribing opioids for pain [33]. This warnings brief assessment tool explores substance abuse history, the • “Losing” prescribed medication on multiple occasions doctor–patient relationship history, antisocial behaviors or a history of such behavior, medication-related behaviors, • Repeatedly seeking prescriptions from other clinicians or personal care and lifestyle issues, need for medicine, and from emergency rooms without informing the original psychiatric and psychosocial issues. prescribing physician The PDUQ is a screening instrument for addictive disease • Showing evidence of deterioration in the ability to in chronic pain patients, which evaluates the pain condition, function (at work, in the family, or socially) that appears opioid use patterns, social and family factors, family history to be related to drug use of pain and substance abuse, and psychiatric history [34].
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Table 3. World Health Organization three-step analgesic ladder. Mild pain (1–4) Non-opioids Acetaminophen ± adjuvants* Nonsteroidal anti-inflammatory drugs Salicylates Propoxyphene Moderate pain (5–6) Weak opioids Codeine ± adjuvants* Hydrocodone Oxycodone plus acetaminophen combinations Tramadol Severe pain (7–10) Strong opioids Morphine (immediate- or sustained-release) ± adjuvants* Oxycodone (immediate- or sustained-release) Hydromorphone Fentanyl transdermal Methadone
*Adjuvants can include anticonvulsants, antidepressants, corticosteroids, dermal analgesics, and muscle relaxants.
The PMQ is a screening tool used to identify patients in of opioid abuse risk have been developed, and are need of more in-depth assessment of risk for opioid misuse, discussed below. and can enable clinicians to determine the appropriateness of opioid treatment [35]. Although its validity needs to be Clinical guidelines to determine further examined, it is a helpful instrument to assist clinicians. treatment strategy One questionnaire developed exclusively for continued The fear of causing addiction and the apprehension of assessment of current opioid use is the Current Opioid prescribing opioids can be barriers to the effective treatment Misuse Measure [36]. This assessment is useful for pain of chronic pain. In this section, clinical guidelines to help patients already on long-term opioid therapy and can be clinicians formulate a plan to facilitate opioid risk used to track patient risk-related status over time. The management are outlined. questions address ongoing medication misuse by asking patients about their current behaviors and cognitions. Selecting an analgesic regimen The three-step WHO ladder for cancer pain has been widely Assessment of pain in the context of addiction used, and adapted for the treatment of chronic non-cancer Distinguishing between opioid abuse and legitimate opioid pain (Table 3) [40]. Step 1 recommends the use of non-opioid dependence for pain remains a challenge. Although most medication, with or without an adjuvant medication if patients do not need escalating opioid doses over time [37], necessary. Adjuvant medications – which include there is a subgroup of individuals in whom tolerance antidepressants, anticonvulsants, and corticosteroids – are used develops, and increasing doses of opioid are required [38]. to enhance analgesic effect, to treat concurrent symptoms that Clinicians are often uncomfortable in this situation and may may exacerbate pain, and to provide an independent analgesic fear medico-legal consequences. When prescribing opioids effect. If pain persists or increases, Step 2 recommends taking for chronic pain, it is important to screen for addiction risk an opioid medication that is used for mild to moderate pain at the start of treatment. With ongoing assessment, a along with a non-opioid medication and an adjuvant clinician may identify a legitimate need for a dose increase medication, if necessary. If pain continues or increases further, versus excessive use of medication in the context of opioid Step 3 recommends taking an opioid medication for moderate abuse. Treatment agreements that outline any consequence to severe pain along with non-opioid medication and an of problematic behavior can be useful for patients to have adjuvant medication, if necessary. an understanding of how issues are managed in special In general, it is best to start with low doses of situations (i.e. what happens when a patient runs out of medication, and to increase the dose slowly to determine medications early, or consequences of urine drug toxicology the optimal level of pain control. Although immediate- found to be positive for other drugs or opioids that are not release formulations (e.g. morphine sulfate immediate prescribed) [39]. This system will allow the patient to know release) are often utilized for acute pain, sustained-release from the start that his or her use of opioid pain medications formulations (e.g. MS Contin [Purdue Pharma LP, Norwalk, will be carefully managed, and that any aberrant behaviors CT], Kadian [Alpharma, Inc., Bridgewater, NJ], Avinza will be addressed. In addition, specific clinical assessments [Ligand Pharmaceuticals, Inc., San Francisco, CA]) prescribed
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at regular intervals should be used for chronic pain. The potency 10-times greater than that of morphine, has a ceiling availability of short-acting opioids should be limited in the effect for treating pain. For patients with severe pain, substance-abusing population owing to risk of misuse buprenorphine may not provide adequate relief. However, for [41,42]. However, recent evidence has shown similar rates those with mild to moderate pain, buprenorphine can be ideal of opioid abuse among patients taking short-acting opioids for the treatment of both opioid dependence and chronic pain. versus long-acting opioids for chronic pain [43]. Advantages Analgesic effects of buprenorphine last approximately 6–8 h, of utilizing long-acting over short-acting opioids in chronic so total daily doses must be divided throughout the day to pain treatment are the provision of longer, continuous provide continuous pain relief. The benefits of buprenorphine periods of pain relief, less peak-and-trough effect, fewer side are its safety, minimal side effects, and decreased liability for effects, better compliance, and less disturbed sleep [44,45]. abuse potential due to its ceiling effect [51]. While tramadol may not provide adequate analgesia for Non-pharmacological therapies including physical moderate to severe pain syndromes, it has been found to be therapy, exercise, behavioral therapy, meditation, and effective for some patients with a milder chronic pain lifestyle change may also be of benefit for pain relief in some syndrome [46]. However, tramadol has been associated with cases, and may be encouraged in combination with opioid seizures and abuse liability, and so caution should be used if or non-opioid therapy. Clinicians should also ensure that higher doses are needed [47,48]. Lidoderm patches (Endo these other treatment options are maximized. Pharmaceuticals, Chadds Ford, PA) are also a good choice for It is advisable for clinicians to employ universal this population, especially in those with musculoskeletal pain. precautions in order to triage individuals to different Adjuvant medications, such as antidepressants and categories (low-, medium-, and high-risk) in terms of anticonvulsants, may help with neuropathic pain. addiction liability [52]. After thoroughly assessing the Desipramine, nortriptyline, and trazodone are preferred patient’s history prior drug and alcohol use, family history of medications due to their minimal side-effect profiles [49]. In any substance abuse, and prior pain management regimens, contrast, selective serotonin reuptake inhibitors have not a clinician can determine what level of risk the patient proved to be beneficial for pain control [50]. represents. Urine toxicology should be consistent if opioids are prescribed (e.g. a patient taking Vicodin [Abbott Opioid maintenance for chronic pain Laboratories, Abbott Park, IL] or Lortab [UCB Pharma, Inc., For most opioids, a dosing schedule of two to four times Smyrna, GA] should have hydrocodone-positive, daily is recommended to provide continuous coverage for oxycodone-negative tests). pain relief throughout the day. Additional, but limited, Low-risk patients with chronic non-cancer pain have no amounts of breakthrough doses should also be available, history of substance abuse and lack any major psychiatric which may help patients gain a greater sense of control over comorbidity. There are no indications of aberrant behaviors pain. After initiation of an opioid, if the pain relief is not in such patients, or any warning signs that they might abuse adequate, an increase in dose can be made after 3 days; medications. These individuals can be managed in a primary subsequent dose titrations can be made in 24-h periods. As care setting. there is an absence of a ceiling effect with full-agonist Medium-risk patients may have a prior history of opioids, doses can be increased until a desired analgesic substance abuse or dependence, family history of substance effect is reached or until side effects are intolerable. abuse, or may have psychiatric comorbidity. These However, increases in doses of methadone should be made individuals can be managed in a primary care setting less frequently, due to its long half-life, which is discussed in particularly with consultation from a specialist (e.g. an the next section. addiction specialist or psychiatrist). High-risk patients are those with active addictive Treatment of chronic pain in substance abusers disorders. These individuals are at an increased risk for Both methadone and buprenorphine are medications available aberrant behaviors and should be referred to a tertiary clinic for the treatment of opioid dependence, and can also be used that specializes in pain management. In this setting, it is for the treatment of chronic pain. These are recommended for recommended that clinicians, together with the patient, patients with a history of substance use, especially opioid prepare treatment agreements that delineate rules such as abuse or dependence. Methadone is a full opioid-agonist with having no early refills and requirements for urine toxicology. a long half-life (17–128 h). Caution should be used when If long-term treatment of chronic pain with opioids is titrating the dose of methadone. It should be prescribed at a indicated, it is important to screen for addiction at the start low dose initially, and then increased slowly to avoid toxicity. of treatment. There are several reliable, well-validated Buprenorphine is a partial opioid-agonist and, despite having a measures that can help determine addiction risk. A careful
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The Mini International Neuropsychiatric part of the decision-making process for their pain Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview. J Clin Psychiatry 1998;59:S22–33. management. Understanding psychological issues, 21. Kroenke K, Spitzer RL. The PHQ-9: a new depression and diagnostic severity measure. spirituality, and support systems can also provide useful Psychiatr Ann 2002;32:509–21. 22. Beck AT, Ward CH, Mendelson M et al. An inventory for measuring depression. Arch Gen information to help tailor treatment. Psychiatry 1961;4:561–71. The use of clinical assessments, urine drug testing, and 23. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62. treatment agreements allow clinicians to treat chronic pain 24. Rosenstiel AK, Keefe FJ. The use of coping strategies in chronic low back pain patients: relationship to patient characteristics and current adjustment. Pain 1983;17:33–44. with more confidence in patients and less fear of increased 25. Jensen MP, Karoly P, Huger R. The development and preliminary validation of an substance abuse. Ongoing evaluations can be beneficial in instrument to assess patients’ attitudes toward pain. J Psychosom Res 1987;31:393–400. 26. Jensen MP, Turner JA, Romano JM et al. The Chronic Pain Coping Inventory: development guiding any change in treatment, and improving the and preliminary validation. Pain 1995;60:203–16. communication between the clinician and patient. By 27. Zimet GD, Dahlem NW, Zimet SG et al. The Multidimensional Scale of Perceived Social Support. J Pers Assess 1988;52:30–41. addressing all of the dimensions of pain, patients can feel 28. Fudala PJ, Bridge TP, Herbert S et al. Office-based treatment of opiate addiction with a that their needs have been fully understood, which will sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med 2003;349:949–58. facilitate effective treatment of chronic pain. 29. Passik SD, Kirsh KL, Whitcomb L et al. A new tool to assess and document pain outcomes in chronic pain patients receiving g opioid therapy. Clin Ther 2004;26:552–61. 30. Jaffe J. Opiates: clinical aspects. In: Lowinson J, Ruiz P, Mullman R, editors. Substance Disclosures Abuse: a Comprehensive Textbook. Baltimore, MD: Williams & Wilkins, 1992:186–94. Drs M Sullivan and J Manubay have no relevant financial interests to 31. Portenoy RK, Payne R. Acute and chronic pain In: Lowinson J, Ruiz P, Millman R, Langrod J, editors. Substance Abuse: a Comprehensive Textbook. Baltimore, MD: Williams & disclose. Dr S Comer serves as a consultant to Cephalon Pharmaceuticals, Wilkins, 1997:563–90. King Pharmaceuticals, and Inflexxion. In addition, she has received funding 32. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-dependent patients: preliminary validation of the opioid risk tool. 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39. Fishman SM, Bandman TB, Edwards A et al. The opioid contract in the management of 46. Schug SA. The role of tramadol in current treatment strategies for musculoskeletal pain. chronic pain. J Pain Symptom Manage 1999;18:27–37. Ther Clin Risk Manage 2007;3:717–23. 40. Management of cancer pain. Management of Cancer Pain Guideline Panel. Clinical 47. Cicero TJ, Adams EH, Geller A et al. A postmarketing surveillance program to monitor practice guideline no. 9. Rockville, MD: US Department of Health and Human Service, Ultram (tramadol hydrochloride) abuse in the United States. Drug Alcohol Depend Public Health Service, Agency for Health Care Policy and Research, March 1994. (AHCPR 1999;57:7–22. publication no. 94-0592.) 48. Jovanović-Cupić V, Martinović Z, Nesić N. Seizures associated with intoxication and abuse 41. Jage J. Opioid tolerance and dependence – do they matter? Eur J Pain 2005;9:157–62. of tramadol. Clin Toxicol (Phila) 2006;44:143–6. 42. Kahan M, Srivastava A, Wilson L et al. Misuse of and dependence on opioids: study of 49. Richeimer SH, Bajwa ZH, Kahraman SS et al. Utilization patterns of tricyclic antidepressants chronic pain patients. Can Fam Physician 2006;52:1081–7. in a multidisciplinary pain clinic: a survey. Clin J Pain 1997;13:324–9. 43. Manchikanti L, Manchukonda R, Pampati V et al. Evaluation of abuse of prescription and 50. Max MB, Lynch SA, Muir J et al. Effects of desimipramine, amitryptyline and fluoxetine on illicit drugs in chronic pain patients receiving short-acting (hydrocodone) or long-acting pain in diabetic neuropathy. N Engl J Med 1992;326:1250–6. (methadone) opioids. Pain Physician 2005;8:257–61. 51. Ciraulo DA, Hitzemann RJ, Somoza E et al. Pharmacokinetics and pharmacodynamics of 44. Portenoy RK. Opioid therapy for chronic nonmalignant pain: a review of the critical issues. multiple sublingual buprenorphine tablets in dose-escalation trials. J Clin Pharmacol J Pain Symptom Manage 1996;11:203–17. 2006;46:179–92 45. Portenoy RK. Opioid therapy for nonmalignant pain: current status. In: Fields HL, 52. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational Liebeskind JC, editors. Pharmacological Approaches to the Treatment of Chronic Pain: approach to the treatment of chronic pain. Pain Med 2005;6:107–12. New Concepts and Critical Issues: the Bristol-Meyers Squibb Symposium on Pain Research. Progress in Pain Research and Management. Vol 1. Seattle, WA: IASP Press, 1994:247–87.
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Risk Assessment for Opioid Misuse in Chronic Pain Treatment
Michael F Weaver, MD1, and Sidney H Schnoll, MD, PhD1,2 1Virginia Commonwealth University, Richmond, VA, and 2Pinney Associates, Westport, CT, USA
Many medications, including opioids, are effective for chronic pain, whether due to cancer or chronic non-malignant pain. However, opioids carry risks of misuse. Universal precautions in pain management involve the use of a medication LEADING ARTICLE agreement and ongoing monitoring such as urine drug testing. Screening for aberrant medication-taking behaviors (AMTBs) with specific screening tools can aid clinicians in stratifying patients according to degree of risk for initiating or maintaining opioids. This helps determine which patients need closer monitoring in addition to universal precautions. AMTBs can be addressed with good communication and recognition of the underlying cause, whether due to addiction, pseudoaddiction, or comorbid psychiatric disorders. Adv Pain Manage 2008;2(2):68–75.
Treatment of chronic pain can be both challenging and usually occurring only in opioid-naïve patients, and is rewarding for practitioners. Judicious use of opioids can antagonized by the presence of pain [3]. bring relief to suffering patients, but opioids are also Opioids have been demonstrated to be effective for associated with risks of misuse that can lead to adverse neuropathic pain [7], failed back surgery syndrome/spinal outcomes for patients. The authors discuss screening for pain [8], osteoarthritis [9], and chronic pancreatitis [10]. potential risks of opioid misuse among patients with chronic However, the average pain reduction attributable to opioids pain, risk stratification of patients, and some strategies to is only 32%, based on a weighted average of results from help reduce the risk of opioid misuse. randomized trials of long-term opioids [11]. Once an opioid has been selected, it should be evaluated for its effectiveness Opioids in chronic pain in controlling the patient’s pain. Ongoing assessment and Currently, because there is no accepted consensus regarding consideration of the need for opioids is required to help the treatment of chronic pain, there is wide variation in achieve adequate pain relief. opioid use, from 3.5% to 33% among populations of patients suffering from different pain problems [1,2]. Other treatments of chronic pain Published consensus statements to guide physicians in the Many non-opioid alternative treatment approaches and prescription of opioids emphasize the importance of a medications are available for the treatment of chronic pain. standardized approach [3,4]. Opioid formulations and Depending on the cause of the pain, the primary medications regimens can be tailored to the patient’s pain pattern, are nonsteroidal anti-inflammatory drugs or anticonvulsants lifestyle, and preference [5]. Following initiation of opioid (carbamazepine, gabapentin, topiramate, or lamotrigine), treatment, dose increases should be achieved within weeks which have proved successful in treating multiple types of and should be moderate. Any further increases in dose chronic pain [12–16]. A newer anticonvulsant, pregabalin, has should be introduced with extreme caution [6]. Tolerance to also been approved by the US Food and Drug Administration the analgesic effects of opioids is variable, but not absolute, (FDA) for specific chronic pain syndromes [17,18]. so no upper limit to the dosage of pure opioid agonists can Furthermore, topical preparations can be effective in the be established. Based on clinical observations, respiratory treatment of chronic pain and include capsaicin [19], lidocaine depression induced by opioids tends to be short-lived, ointment or patch [20], and nonsteroidal anti-inflammatory agents [21,22]. Some antidepressants can act as analgesic Address for correspondence: Michael F Weaver, Associate Professor of agents. Tricyclic antidepressants (e.g. amitriptyline, Internal Medicine and Psychiatry, Virginia Commonwealth University, nortriptyline) [23] have been widely used for different types 1200 East Broad Street, 11th Floor, Room 1141, PO Box 980109, of chronic pain and bupropion may be effective in certain Richmond, VA 23298–0109, USA. Email: [email protected] types of neuropathic pain [24]. Norepinephrine–serotonin
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Table 1. Cancer and chronic non-malignant pain. Characteristic Cancer pain Chronic non-malignant pain Terminal diagnoses Typically yes No Time course of treatment <12 months Maybe decades Time to achieve adequate management Often only weeks Maybe years Diagnosis based on tissue or serological testing Yes Usually no Diagnostic diversity Relative homogeneity of conditions Diverse diagnoses and syndromes Practitioner diversity Relative homogeneity of practitioners Diverse group of generalists and specialists in disparate fields Origin of pain type, as often viewed by practitioners Somatogenic Psychogenic Treatment consistency Approach to management No consensus on treatments Maladaptive coping behaviors by patients Less likely More likely
reuptake inhibitor antidepressants such as venlafaxine help Aberrant medication-taking behaviors reduce pain in addition to their antidepressant effects [25], Adequate treatment of chronic pain remains challenging, and duloxetine has FDA approval for the treatment of specific and even cancer pain is often undertreated [28]. Research neuropathic pain diagnoses [26]. Selective serotonin reuptake on abuse liability in opioid therapy has little consistency inhibitors are beneficial for the treatment of the depression across populations of chronic pain patients, nor do the that often accompanies chronic pain. definitions of terms such as abuse and addiction [29]. Non-pharmacological treatments for chronic pain include Aberrant medication-taking behavior (AMTB) is a physical therapy, a program of gradually progressive daily spectrum of patient behaviors involving taking medication in exercise, transcutaneous electrical nerve stimulation, a manner other than that prescribed. The term AMTB is biofeedback, chiropractic manipulation, and acupuncture. A applied to problematic use of medications prescribed for multimodal approach, which may utilize combinations of pain, especially controlled substances, and can include opioid and non-opioid therapies, enhances treatment unauthorized dose escalation, dangerous medication efficacy in many cases. A multidisciplinary approach to combinations (from multiple prescribers or with alcohol/illicit chronic pain utilizing both pharmacological and non- drugs), and “doctor shopping” (visiting multiple physicians pharmacological treatment modalities, including concurrently to obtain controlled substance prescriptions) psychosocial support, is most effective and provides [30]. There is little agreement between physicians about comprehensive care. AMTB beyond the view that illegal behaviors among pain patients are of concern [31]. The presence of AMTB is not Cancer pain and chronic non-malignant pain synonymous with abuse or addiction, although Ballantyne It is important to recognize that there should be a difference and Mao suggest that AMTB is commonly a manifestation between the approach to the management of cancer pain of addiction [5]. AMTB is occasionally a manifestation of and that of chronic non-malignant pain (CNMP), especially inadequate analgesia (pseudoaddiction) and normal regarding the use of opioid analgesics (Table 1). This helps behavior is resumed when pain is adequately treated. Often practitioners and patients avoid frustration that can arise AMTB is motivated by the patient’s desire to manage their from attempting to use a one-size-fits-all approach in pain, but those with comorbid psychiatric disorders may different populations [27]. Some of the early studies in pain misuse opioid analgesics to treat symptoms of depression, management involved cancer pain, and thus there are data anxiety, or personality-related disturbances [32]. from which best practice guidelines can be derived. Evidence- A physician’s perception of AMTB may be different from a based guidelines for cancer pain management have been patient’s perception, and physicians may feel uncomfortable accepted and updated over the past two decades. CNMP asking directly about problem behavior or illegal activity [33]. management was initially guided by research on patients Past behavior predicts future performance, and a known with cancer pain. Malignancy survivors may develop CNMP history of illicit drug use and a young age are the strongest from complications of cancer or its treatment and, conversely, predictive factors for AMTB, even more so than pain variables patients with CNMP may develop cancer or other conditions [34,35]. Early awareness of AMTB and subsequent physician that should not be overlooked by attributing their symptoms action can disrupt behavioral patterns of medication misuse to CNMP until it is too late. and addiction, and thus improve treatment outcomes.
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MICHAEL F WEAVER AND SIDNEY H SCHNOLL
Table 2. Screening tools for risk of opioid misuse in patients with chronic pain. Instrument name Format Items Population studied Prediction
PMQ [55] Self-administered 26 Patients with chronic Higher scores associated with a history of substance (written) pain at one pain center abuse, higher levels of psychosocial distress, and poorer functioning
ORT [56] Self-administered 5 Patients with chronic High sensitivity and specificity for determining (written) pain at one pain center patients at risk of opioid-related AMTB SOAPP [57] Self-administered 24 Patients with chronic High-risk associated with young age and (written) non-malignant pain at abnormal urine drug screens two pain centers SOAPP-R [58] Self-administered 24 Patients with chronic Low-score patients are least likely to develop a (written) non-malignant pain at substance use disorder multiple pain centers PDUQ [59] 20-min interview 42 Patients with chronic Higher score differentiates those who meet by clinician pain at one pain center criteria for substance use disorder DIRE [60] Completed by 7 Patients with chronic Good correlation with patient compliance, clinician pain at one pain center moderate correlation with opioid efficacy PADT [49] Interview by clinician 41 Multiple primary care and Improves the ability of clinicians to detect pain specialist practices problem behaviors ABC [45] Clinician observation 20 Patients with chronic Assists clinicians in tracking AMTB over time over time pain at one pain center COMM [46] Self-administered 40 Patients with chronic Detects AMTB in patients already on (written) pain at one pain center chronic opioids
ABC: Addiction Behaviors Checklist; AMTB: aberrant medication-taking behavior; COMM: Current Opioid Misuse Measure; DIRE: Diagnosis, Intractability, Risk, and Efficacy score; ORT: Opioid Risk Tool; PADT: Pain Assessment and Documentation Tool; PDUQ: Prescription Drug Use Questionnaire; PMQ: Pain Medication Questionnaire; SOAPP: Screener and Opioid Assessment for Patients with Pain; SOAPP-R: Revised SOAPP.
Screening controlled substance prescriptions. Screening tools should It is important to screen all patients for the risk of opioid not be used as a means of denying care to patients at high misuse before starting long-term opioid therapy for chronic risk, but to indicate a need for caution in the use of long- pain [36]. Tools have been developed to help providers term opioid therapy. Non-opioid adjunct pain management determine which patients are likely to require more intense modalities may be utilized initially, followed by a trial of monitoring while taking long-term opioids for chronic pain opioids with close monitoring, and assistance from an (Table 2). To date, no research has been conducted appropriate pain or addiction specialist may be sought. to establish which instrument is best for predicting opioid misuse in patients with chronic pain [37]. Those Risk stratification that have been validated have only been so in small The ethical principles of beneficence and justice require that populations in specialist pain management centers, usually all patients have equal access to pain management, but can at only one site and rarely in a primary care population. conflict with the principle of non-maleficence when AMTBs Most rely on patient self-report of behaviors using a brief may result in harm to the patient [38]. The available data on questionnaire or a clinical interview, but this may result in risk assessment in medically ill patients with pain are very significant under-reporting of problem behaviors without limited [39]. Higher risk is not the same as addiction, but collateral information. rather signifies a higher chance of an undesirable outcome of Use of a screening tool to identify a higher level of risk long-term opioid therapy or that the patient will not with regard to opioid misuse helps predict potential significantly benefit from opioids in terms of definitive problems with medication management in that particular functional improvement. A patient identified to be at a high- patient at that time. Being categorized as high risk does not risk level will need thorough evaluation and close monitoring. mean that the patient will definitely demonstrate egregious Some predictors of higher risk have been identified in AMTB or develop addiction, and a low-risk score does not various research studies. The strongest predictor is a history mean that the patient will never have difficulties with of substance abuse, especially polysubstance abuse,
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RISK ASSESSMENT FOR OPIOID MISUSE IN CHRONIC PAIN TREATMENT
Table 3. Levels of risk for opioid misuse in patients with chronic pain. Characteristic Low Moderate High Substance use disorder None current or past Past history Active Cigarette smoking Never Past Current Family addiction history None Significant Significant Psychopathology No major diagnoses, minor Past major diagnosis, current Current major diagnosis diagnoses treated/stable issue with minor diagnosis untreated/unstable Age Older N/A Younger Childhood sexual abuse No N/A Yes Lost or stolen controlled No N/A Yes substance prescriptions Urine drug testing for Consistently negative Positive on initial evaluation Consistently positive unauthorized substances Management setting Primary care Primary care with specialist support Specialty pain management
although significant single substance use includes current Monitoring strategies tobacco smoking and a history of cocaine use [37]. Other Universal precautions predictors include young age [40,41], history of legal As there is no definitive test to predict which patients will do problems (especially charges for drug possession and driving well with a therapeutic trial of opioids for chronic pain, it under the influence) [40,41], and childhood sexual abuse seems logical to take a “universal precautions” approach to [37]. A history of lost/stolen controlled substance all patients [44]. This reduces stigma, improves patient care, prescriptions [40,42], or obtaining controlled substance and reduces risks. Universal precautions include asking prescriptions from sources other than the primary pain patients about personal and family history of substance management physician (e.g. “doctor shopping”, buying on abuse (often using screening tools), obtaining informed the black market, or taking from a friend or family member) consent for treatment (usually with a formal written also correlate with opioid misuse [37]. History alone is treatment agreement), ongoing reassessment of benefits usually insufficient to predict risk accurately, and should be from a trial of opioid therapy, and complete documentation combined with collateral information from significant others of the evaluation and reassessments. and previous healthcare providers as well as urine drug Basic monitoring efforts involve obtaining pharmacy testing (UDT) [43]. records on a routine basis or sending regular inquiries to a Based on initial evaluation of patient characteristics and state prescription monitoring program (PMP), keeping track behaviors, often using screening tools, a level of risk for of the time elapsed between clinic visits, counting the future opioid misuse can be identified. Patients can be medication units that have been prescribed, and random stratified into three groups (low, moderate, and high) based UDT (Table 4) [43]. Escalating pain medication doses is a on their level of risk (Table 3) [44]. This categorizing assists sign that should prompt closer monitoring of medication the clinician in determining the appropriate intensity of use by the physician. While universal precautions are monitoring when starting a therapeutic trial of long-term appropriate for all patients on opioids, screening tools opioids for chronic pain. On the continuum of pain and should be used to help determine in advance which patients addiction, patients may move from dominance of one are likely to need even closer monitoring. For example, a disorder to the other over time, and thus the level of risk patient at low risk may only need to be assessed using may change after the initial assessment [44]. Some of the universal precautions initially, such as at least one random screening tools, specifically the Addiction Behaviors Checklist UDT in 12 months, a query to the PMP once in 12 months, [45] and the Current Opioid Misuse Measure [46], were and counting of pills at each visit. In contrast, a patient at designed to evaluate patients taking chronic opioids over high risk may undergo UDT at nearly every visit initially, pill time for determination of AMTB. Ongoing reassessment, counts and UDT on short notice between visits, and queries including evaluation of whether therapeutic goals have been to the PMP every 1–2 months. The enhanced monitoring is met, helps determine changes in the level of risk over time not to “catch the patient in the act”, but to deter the and the appropriate level of monitoring in addition to basic occurrence of AMTB and assist the patient in achieving universal precautions. adequate treatment. The goal for long-term treatment with
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Table 4. Strategies for physicians to reduce opioid misuse by patients with chronic pain. • See the patient as often as needed, based on the level of medication management demonstrated – Prescribe sufficient pain medication at each visit to last until the next scheduled appointment • Have the patient bring in any remaining medication in the original containers dispensed by the pharmacy – Count the remaining pills/patches to determine the rate at which the patient is using the medication – Check date filled, amount dispensed, and dosing frequency as instructions on the label from the pharmacy • Limit the patient’s sources for controlled substance prescriptions – Only one prescriber for all controlled substance prescriptions – Only one pharmacy at which to fill controlled substance prescriptions • Perform UDT – Confirm adherence with verification of prescribed medications – Test for the presence of illegal drugs or controlled substances not prescribed by the physician managing the patient’s pain • Call the patient in on short notice periodically – Count pills/patches – Perform random UDT • Communicate with the patient’s significant others and/or employer after first obtaining permission to do so • Document any concerns about aberrant medication-taking behavior, along with the plan for following up on such concerns
UDT: urine drug testing.
opioids should be overall improvement in function, not just of legal and regulatory requirements for controlled reduced pain intensity. This can be assessed with the “4 As” substances prescribed in the treatment of pain allows of pain medicine: analgesia, activity, adverse effects, and practitioners to focus on quality medical care and preserve AMTB [47]. patient access to controlled substances [50]. Good communication and honesty between physician Medication agreements usually specify parameters for and patient are essential for a successful outcome in the adherence, means by which adherence will be monitored, treatment of chronic pain. Figure 1 provides an algorithm for and general goals of treatment. In a recent study, the prescription of opioids in patients with chronic pain. No monitoring adherence was associated with a 50% reduction single approach is guaranteed to benefit all patients, so in opioid abuse among patients in chronic pain management practitioners must continually assess each individual patient settings [51]. Adherence monitoring is carried out by for benefit and harm. obtaining an appropriate history and using an initial medication agreement to communicate the parameters for Medication agreement periodic evaluation of appropriate medication use, random As a prerequisite for receiving controlled substance drug testing, and pill counts. prescriptions, a medication agreement reinforces the A medication agreement outlines both what the patient patient’s responsibility, and the patient is reassured that can expect from the physician and what the physician honoring the agreement will result in continued provision of expects from the patient. For less serious problems, such as a adequate amounts of pain medication [48]. Although small, unauthorized dose escalation or single slip of using an sometimes called a contract, a medication agreement is not unauthorized substance, it is important to initiate closer intended to be a legally binding document but a monitoring with more frequent visits and tighter limits on communication tool. Such an agreement clarifies boundaries the amount of medication available at any given time. In and makes possible early identification and intervention for addition, referral for specific addiction treatment may be AMTB. Quality medical care is supported by appropriate appropriate. Repeated violations of the medication documentation of progress of therapy over time, which can agreement or patient refusal to adhere to all aspects of an be enhanced by the use of templates and forms. An addiction treatment program should result in loss of the example of an instrument that has been developed for this privilege of receiving controlled substance prescriptions, but purpose is the Pain Assessment and Documentation Tool does not necessarily indicate that treatment should be (PADT) [49]. In addition to using such a tool, an understanding stopped altogether [29].
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Figure 1. Algorithm for chronic pain management.
Patient with chronic pain
Full diagnostic assessment – assess for history and family history of substance abuse and mental illness
Use screening tools if desired
Physical therapy and other Problems No problems non-opioid therapy
No opioid Opioids Opioid agreement Opioids No opioid
• Continue to monitor pain Analgesic and functional • Continue to monitor pain • Non-opioid therapy improvement • Non-opioid therapy
No Yes • Stop opioid Has AMTB Continue opioid • Start other therapy
• Stop opioid • Continue opioid Continued AMTB No new AMTB • Non-opioid therapy • Intensify monitoring
Refer to substance Continue opioids Continue opioid abuse therapy with caution
AMTB: aberrant medication-taking behavior. Adapted with permission from [30].
UDT must be considered in addition to a UDT result when making UDT detects the presence of prescribed medications and decisions about the pain management plan. The most identifies substances that should not be present in the urine. commonly used UDT is by immunoassays, but monitoring of a Such a test is objective and enhances the physician–patient specific class of drug by immunoassay alone becomes relationship by providing documentation of adherence to the impossible when a patient has been prescribed a drug from that treatment plan for pain management. Urine is the preferred class. Confirmatory testing for specific drugs is necessary to use biological specimen because most substances are detectable for UDT to the best advantage in pain management, and a positive 2–4 days and collection is relatively non-invasive [52]. UDT is immunoassay result in a general class should be specifically most effective in pain management when carried out randomly. identified by gas chromatography/mass spectroscopy. Physicians should be knowledgeable about UDT methods Evaluation of urine temperature, pH, and creatinine levels can and how best to utilize the results. UDT results in the setting of help detect adulteration or substitution of the sample. pain management should be interpreted with caution, which Abnormal or unexpected results should be discussed with the can be facilitated by the physician having a good working patient in a supportive manner with the goal of encouraging relationship with the UDT laboratory. Other clinical information appropriate patient behavior. Documentation should
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demonstrate a clear relationship between UDT results and successfully met clinical goals supports continuation of subsequent actions by the treatment provider. An isolated UDT therapy. Failure to meet goals requires re-evaluation and a result that is positive for an illicit drug or unauthorized change in the treatment plan. This may include closer medication may prompt closer monitoring with more frequent monitoring with more frequent office visits, more frequent UDT; recurrent positive results should encourage referral to an UDT, and random pill counts and UDT on short notice addiction specialist for evaluation. between visits (Table 4). Continuation of AMTB despite A standardized approach reduces stigma and improves discussions of problem behavior should prompt consideration patient care. The initial evaluation is the best opportunity to of tapering off opioids completely. Egregious behavior such discuss the purpose of UDT. When uniformly applied, it is the as forging prescriptions or evidence of drug diversion may exception rather than the rule that a patient with pain is result in immediate loss of the patient’s privilege to receive offended by a request for UDT [53]. Providers can enhance controlled substance prescriptions. acceptance of UDT by explaining that each UDT is an If addiction is diagnosed, instead of immediate opportunity to demonstrate appropriate adherence and build termination of pain management, the physician can discuss up “good credit”. In the case of a future disputed UDT result, with the patient the reasons for the addiction and help this allows the provider to more easily justify giving a patient develop strategies to avoid a relapse [54]. This may include who has a history of good adherence the benefit of the doubt. a trial of continuation of opioids, but with close monitoring. Some cases may require tapering off opioids or immediate Dealing with AMTBs discontinuation due to concerns for the safety of the Whatever the cause of opioid misuse, it may lead to patient regarding serious medication abuse, or legal and unfavorable consequences for both the patient and the licensing concerns for the physician regarding prescribing provider. Consequences to patients include a higher risk of medications that may be diverted. However, discharging unintentional injury due to impaired judgment while the patient from the practice because of addiction problems intoxicated, discomfort from acute withdrawal symptoms, does not solve the underlying problem. The physician may cigarette burns while oversedated, and significant morbidity choose to continue to see the patient and provide other and even mortality from accidental overdose. Family forms of pain treatment without controlled substance members of patients may also suffer consequences, prescriptions [43]. including anguish from concern and frustration with the patient’s behavior, and financial burden from lost income Conclusion due to functional decline or cost of medications. Opioids can be highly beneficial for the treatment of many Consequences to providers include licensing issues and legal different types of chronic pain. However, high-risk patients liability for an adverse outcome. require intense monitoring, and continued problem behavior Regardless of the type of pain being treated, clear may result in loss of the privilege to receive opioids. If addiction communication between the prescribing physician and patient is diagnosed, collaboration with appropriate specialists can is essential for effective administration of opioids. Expectations assist the patient to achieve appropriate function and pain for appropriate patient behavior and medication management relief with a lower risk of significant harm. should be stated at the outset, along with examples of what is not permissible. A written medication agreement helps clarify Disclosures these expectations and the practitioner can refer back to this Dr M Weaver has served on the Speaker’s Bureau for PriCara and the document if the patient displays AMTB in order to reinforce Advisory Board for Cephalon, Inc. Dr S Schnoll has received consulting appropriate behavior and discourage problem behaviors. fees from Cephalon, Inc., Endo Pharmaceuticals, Javelin Strong suspicion of addiction to prescription opioids or illicit Pharmaceuticals, MEDA AB, and Purdue Pharma LP. drugs should prompt the prescriber to discuss these concerns openly with the patient. Referral to an addiction specialist is References encouraged to definitively diagnose addiction or to confirm 1. 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Curr Med Res Opin 2008;24:925–50. controlled substance abuse in chronic pain patients? Pain Physician 2006;9:57–60. 23. Onghena P, Van Houdenhove B. Antidepressant-induced analgesia in chronic non- 52. Caplan YH, Goldberger BA. Alternative specimens for workplace drug testing. J Anal malignant pain: a meta-analysis of 39 placebo-controlled studies. Pain 1992;49:205–19. Toxicol 2001;25:396–9. 24. Semenchuk MR, Sherman S, Davis B. Double-blind, randomized trial of bupropion SR for 53. Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage the treatment of neuropathic pain. Neurology 2001;57:1583–8. 2004;27:260–7. 25. Sindrup SH, Bach FW, Madsen C et al. Venlafaxine versus imipramine in painful 54. Miotto K, Compton P, Ling W et al. Diagnosing addictive disease in chronic pain patients. polyneuropathy: a randomized, controlled trial. Neurology 2003;60:1284–9. Psychosomatics 1996;37:223–35. 26. Raskin J, Pritchett YL, Wang F et al. 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Patient Affected by Severe Cancer Pain and Treated with Combined Strong Opioids
Elena Catala, MD, PhD, Analia Azaro, MD, and Marta Ferrandiz, MD University Hospital Santa Creu i Sant Pau, Barcelona, Spain
CASE STUDY Cancer pain is one of the most important challenges for pain specialists and doctors treating cancer patients. In this patient population pain can be the cause of reduced quality of life. For this reason treating pain early on in the disease and aggressively is one of the goals of care. The authors describe a patient with multiple myeloma who developed nociceptive and neuropathic pain, which was controlled with the addition of a second strong opioid and an anticonvulsant to her existing treatment regimen. Adv Pain Manage 2008;2(2):76–78.
Case Study with only slight sedation remaining, which was accompanied The patient was a 67-year-old female who presented to the by a considerable improvement in QoL. Later on she pain clinic with low back pain and was diagnosed with experienced a sudden onset of shooting lumbar pain that multiple myeloma. X-ray carried out at the initial evaluation she described as severe (VAS 9), continuous, and sharp, showed multiple osteolytic skeletal lesions and a focalized which radiated down her left leg. Magnetic resonance lesion in lumbar vertebrae. Low back pain was severe – she imaging (MRI) and a bone scan of the lower back confirmed reported a pain intensity score of 8 on a visual analogue multiple compression fractures on lumbar vertebrae L3 and scale (VAS; 0–10) – and continuous, and increased with L4 and myeloma invasion of the lumbar spine. The walking and standing. Laboratory assessment showed treatment strategy involved radiotherapy of the lumbar anemia, an erythrocyte sedimentation rate of 98 mm/h, and region and the addition of pregabalin to her treatment a serum protein level of 92 g/L. Protein electrophoresis regimen, which was titrated up to 150 mg twice daily with revealed a monoclonal band in the γ region. The band was an adjustment of the oxycodone ER dose to 30 mg twice analyzed and shown to be IgG of λ type. Serum albumin, daily and continuation of the same dose of morphine. At creatinine, and urea levels were normal but her serum day 10 after this strategy was implemented the patient calcium level was elevated. reported an improvement in the control of her pain (VAS 4), For treatment of multiple myeloma, the patient was with minor side effects. started on dexamethasone and lenalidomide. She was also given intravenous bisphophonates and, for pain relief, oral Discussion morphine at an initial dose of 10 mg twice daily titrated to As patients with cancer now live longer than they did in the 40 mg twice daily. Over the following 2 months the dose of past, the need for effective pain control has become more oral morphine was increased to 80 mg twice daily. Her pain important, with pain often being the cause of low QoL in was better controlled (VAS 4) but side effects, such as this population [1]. The incidence of pain varies according to sedation, emesis, and fatigue, considerably reduced her the type of neoplasm, as well as the stage of the disease [2]. quality of life (QoL). Instead of rotating opioids, another Nociceptive pain secondary to invasion of bone is the most long-acting, potent, opioid – oxycodone extended release common type of pain in patients with hematological (ER) – was added to her treatment regimen. During the next malignancies. The pain is typically constant as well as 5 months the patient was given morphine 40 mg and exacerbated by movement of the affected area, and is most oxycodone 20 mg, both twice daily. Her VAS score stabilized commonly localized in the spine. In addition, associated at around 2–3 and the side effects decreased significantly, radicular pain often develops. It is crucial to identify the type of pain and the underlying physiopathology in order to offer Address for correspondence: Elena Catala, Pain Clinic, Anesthesiology the patient the best possible treatment. service, Hospital Santa Creu i Sant Pau, St Antoni Maria Claret 167, Multiple myeloma can present a challenge to the 08025 Barcelona, Spain. Email: [email protected] practitioner due to the diversity of pain syndromes, both
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nociceptive (caused by osteolysis and bone marrow rescue drug was oxycodone immediate release rather than expansion) and neuropathic (caused by nerve damage), morphine immediate release [9]. These findings suggest that experienced during the course of the disease. The patients who develop side effects during opioid titration mechanism of pain due to osteolysis is multifactorial and might benefit from the addition of a second opioid with a involves direct osteolytic damage of the bone, bone different receptor affinity profile at a low dose. However, fractures, mechanical instability, and a reduction in the caution should be exercised when selecting opioids for their nociceptor threshold caused by the local release of synergistic effect because synergism has been observed cytokines, potassium, histamine, and other substances. Bone across the board for all opioids. Bolan et al. demonstrated in marrow expansion by malignant infiltration and tumor animal models that while methadone showed a synergistic growth causes an increase in intraosseus pressure and effect with both morphine and codeine, morphine only activates the periosteum, which produces substances synergized with methadone [8]. In the present case, the responsible for reducing the nociceptor threshold. addition of low-dose oxycodone to a dose of morphine that Neuropathic pain can be caused by secondary amyloid was causing CNS-mediated side effects resulted in infiltration of neural tissue, nerve compression, or the direct remarkable improvement in the control of nociceptive pain action of paraproteins produced by the myeloma itself [3]. and tolerability. Opioid analgesics are the first-line therapy for the Synergism has also been observed when certain opioids treatment of somatic pain in cancer patients [4]. Most exert have been combined with other adjuvant analgesics. In a their analgesic action through the activation of μ opioid crossover study, Keskinbora et al. reported synergism receptors. Among this group of analgesics, the most between oxycodone ER and pregabalin [10]. In the present commonly utilized is morphine. Oxycodone, another high- case, a marked improvement in analgesia was observed potency opioid, binds to the κ subtype in addition to when pregabalin was added to treat neuropathic pain possessing affinity for μ opioid receptors. Indeed, it has been symptoms, suggesting that synergism did occur. proposed that the intrinsic analgesic effect of oxycodone is Neuropathic pain is caused by changes in the central and mediated through the activation of κ opioid receptors [5]. Full- peripheral nervous systems [11]; treatment is challenging agonist opioids, such as morphine, oxycodone, fentanyl, because of its severity and resistance to most analgesics methadone, and oxymorphone, can be titrated to effectiveness [12]. Diagnosis of the disorder is based primarily on clinical regardless of their potency because they do not have a ceiling history (type of tumor and distinct pain qualities) and effect. The limiting factor is usually the development of side physical examination. In cancer pain patients, MRI and bone effects (e.g. constipation, sedation, nausea) that cannot be scans can be helpful diagnostic tools (e.g. in identifying the successfully managed, or the development of tolerance of the presence of compression fractures or nerve enhancement analgesic effect. The strategy usually recommended to indicative of infiltration). The treatment of neuropathic pain overcome these two major limiting factors is opioid rotation. often requires adjuvant analgesics such as pregabalin or The rationale is that the presence of side effects or tolerance of gabapentin, as well as the addition of high-potency opioids. one opioid does not imply the presence of side effects or In order to achieve the full effect, strong opioids are used tolerance of another. Hence, through rotation, effectiveness frequently, as indicated by recent studies [10,13]. can be recovered and tolerance reduced. However, this This case report highlights several interesting and strategy it is not always successful. provocative points related to opioid-to-opioid and opioid-to- The observation that the combination of two opioids adjuvant medication synergism, but has several limitations. with different spectrums of receptor affinity may result in Firstly, after achieving the maximum tolerated dose of synergism in terms of the analgesic response, rather than morphine, rather than carrying out opioid rotation and summation of the individual effects [6], and in a reduction in switching to another, oxycodone was added to the the development of tolerance has generated much morphine dose. The possibility that oxycodone alone at that excitement. Preclinical studies have shown that the dose would have induced sufficient pain relief cannot be combination of morphine and oxycodone [7], methadone ruled out, nor can the possibility of a summation effect. and morphine [8], or methadone and codeine [8] results in a However, the equianalgesic ratio of oxycodone is higher synergistic analgesic effect with a low incidence of central than the dose given to this patient, suggesting the presence nervous system (CNS) side effects. The synergistic effect of synergism. The same limitations apply to the addition of between morphine and oxycodone was later corroborated pregabalin. Although the low dose and the dramatic pain by a randomized, controlled, clinical trial. Lauretti et al relief experienced by the patient suggests the presence of observed that patients treated with morphine ER utilized less synergism with the opioids, the possibility that pregabalin rescue medications and had fewer side effects when the alone would have been sufficient to control neuropathic pain
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cannot be ruled out, as this regimen was not tried due to the 2. Davis MP, Walsh D. Epidemiology of cancer pain and factors influencing poor pain control. Am J Hosp Palliat Care 2004;21:137–42. complexity of the patient’s multiple pain syndromes. 3. Niscola P, Arcuri E, Giovannini M et al. Pain syndromes in haematological malignancies: an overview. Hematol J 2004;5:293–303. 4. Binhas M, Krakowski I, Marty J. Nociceptive cancer pain in adult patients: statement about Conclusion guidelines related to the use of antinociceptive medicine. Ann Fr Anesth Reanim The observations of this case report support the notion that 2007;26:502–15. 5. Ross FB, Smith MT. The intrinsic antinociceptive effects of oxycodone appear to be kappa- a combination of two opioids with different profiles of opioid receptor mediated. Pain 1997;73:151–7. receptor affinity may result in better pain relief in a selected 6. He L, Fong J, von Zastrow M et al. Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization. Cell 2002;108:271–82. group of patients in whom the primary opioid cannot be 7. Ross FB, Walls SC, Smith MT. Co-administration of sub-antinociceptive doses of uptitrated due to side effects. It has been speculated that oxycodone and morphine produces marked antinociceptive synergy with reduced SNC side-effects in rats. Pain 2000;84:421–8. synergism occurs due to the different profiles of receptor 8. Bolan EA, Tallarida RJ, Pasternak GW. Synergy between mu opioid ligands: evidence for affinity but the underlying mechanism has not yet been functional interactions among mu opioid receptor subtypes. J Pharmacol Exp Ther 2002;303:557–62. elucidated. Large controlled studies need to be conducted to 9. Lauretti GR, Oliveira GM, Pereira NL. Comparison of sustained-release morphine with clarify which opioids have this potential. sustained-release oxycodone in advanced cancer patients. Br J Cancer 2003;89:2027–30. 10. Keskinbora K, Pekel AF, Aydinli I. Gabapentin and an opioid combination versus opioid alone for the management of neuropathic cancer pain: a randomized open trial. J Pain Disclosures Symptom Manage 2007;34:183–9. 11. Jensen TS, Gottrup H, Sindrup SH et al. The clinical picture of neuropathic pain. Eur J The authors have no relevant financial relationships to disclose. Pharmacol 2001;429:1–11. 12. Dworkin RH, O’Connor AB, Backonja M et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007;132:237–51. References 13. Gore M, Sadosky A, Tai KS et al. A retrospective evaluation of the use of gabapentin and 1. Tavioli A, Montazeri A, Roshan R et al. Depression and quality of life in cancer patients pregabalin in patients with postherpetic neuralgia in usual-care settings. Clin Ther with and without pain: the role of pain beliefs. BMC Cancer 2008;21:177–85. 2007;29:1655–70.
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CLINICAL REVIEWS Commentary and Analysis on Recent Key Papers
Clinical reviews were prepared by Lara Dhingra, PhD, Helena Knotkova, PhD and E Alessandra Strada, PhD
NEUROPATHIC PAIN Health Survey Questionnaire-36. Adverse events associated with pregabalin treament included nausea, decreased cognitive performance, somnolence, dizziness, confusion, Pregabalin in patients with central neuropathic pain: and peripheral edema. a randomized, double-blind, placebo-controlled trial The authors noted that the reductions in the pain scores in of a flexible-dose regimen the pregabalin group were only modest, thus clinical Vranken JH, Dijkgraaf MG, Kruis MR et al. importance of observed pain relief might be debatable. Pain 2008;136:150–7. However, the refractory nature of central pain and specific pain characteristics of the sample (severe chronic pain resistant to In this trial, including patients with central neuropathic various pharmacological treatments) should be kept in mind. In pain due to brain- or spinal-cord injury, pregabalin was conclusion, this study demonstrates the analgesic efficacy of found to significantly reduce pain in clinical settings, pregabalin and indicates its potential use for central improving health status, compared with placebo. neuropathic pain therapy. 1. Gilron I, Flatters SJ. Gabapentin and pregabalin for the treatment of neuropathic pain: a review of laboratory and clinical evidence. Pain Res Manag 2006;11:16–19A. Pregabalin has recently been reported to possess 2. Siddall PJ, Cousins MJ, Otto A et al. Pregabalin in central neuropathic pain associated with antihyperalgesic and anti-allodynic properties in various animal spinal cord injury. Pain 2003;103:249–57. models, and to be effective in the treatment of non-malignant Address for reprints: JH Vranken, Pain Relief Unit, Academic Medical chronic neuropathic pain [1,2]. In this randomized, double- Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, blind, placebo-controlled trial, the investigators evaluated the The Netherlands. Email: [email protected] effects of pregabalin on pain, tolerability, health status, and quality of life in patients with central neuropathic pain. A randomized, placebo-controlled, crossover A sample pool of 76 patients with central neuropathic trial of cannabis cigarettes in neuropathic pain pain due to brain- or spinal cord injury, were screened for Wilsey B, Marcotte T, Tsodikov A et al. the study. Of these, 40 subjects met the study criteria and J Pain 2008;9:506–21. were randomized to receive either pregabalin at doses of 150, 300, and 600 mg/day (n=20) or placebo (n=20). The In this rigorous study of patients suffering from neuropathic majority of patients – 17 in the pregabalin group and pain, the pain intensity and pain discomfort (a measured 16 patients in the placebo group – completed the study. subjective response to pain), were evaluated and evidence At the end of the study, the primary efficacy measure of a beneficial effect of smoking herbal cannabis was (reduction in mean endpoint pain visual analogue scale provided. Measures of the degree of pain relief on a global [VAS] score) changed significantly in the pregabalin group impression of change scale also showed improvement. compared with the placebo group. Mean pain intensity VAS scores before and after 4 weeks of treatment in the Many patients, in particular those with neuropathic pain, use pregabalin group decreased from 7.6 to 5.1 (p=0.01), cannabis for medicinal purposes, despite the fact that whereas in the placebo group the change was not medicinal use has not been scientifically validated for significant, with a reduction from 7.4 to 7.3. In addition, in this drug. The authors carried out a double-blind, placebo- the pregabalin group but not in the placebo group, there controlled, crossover study in 38 patients with neuropathic were significant improvements in health status as measured pain to assess whether smoking cannabis could cause an by the EQ-5D and in the bodily pain subscale of Short-form improvement in pain.
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Significant analgesia was observed equally with use of this study, the authors use their previously validated high- and low-dose cigarettes within 4 h, with a probable questionnaire based on pain descriptors to estimate the onset of relief in 1 h. The analgesic effect began to reverse prevalence of chronic pain with or without neuropathic 1–2 h after the last dose. As noted in some prior studies [1,2], characteristics (NC) within the French population. Although there was no effect on allodynia or evoked pain. identified NC are similar to those present in patients with Reports of psychoactive effects (“feeling high or neurological lesions, without clinical information neuropathic stoned”) and “feeling impaired” were noted. Calmness was pain could be mistakenly defined. noted with the use of low-dose cigarettes, whereas an More than 80% of the French population responded to increase in anxiety was observed with use of the high dose. the survey, including nearly 20% who reported chronic pain A decline in all measures of cognitive function was seen with of moderate to severe intensity, and of these >25% reported use of the high dose, and the low dose showed impaired NC. This percentage is substantially greater than recent verbal learning and recall. A recovery trend was noted 2 h estimates of the prevalence of neuropathic pain, but is after the last dose was taken. consistent with findings from a recent extensive population Treatment was regarded as well tolerated with a “good survey in the UK [1]. drug effect”, as measured using a 100-mm visual analogue In manual workers, the odds ratio was double for chronic scale. The impairment in neuropsychological function and pain with NC compared with those without NC. In this mood changes, especially in the higher-dose trial, was not population, pain was experienced in multiple locations (two significant. Supporting this, the authors reported that no sites in 38% and three sites in 30%), with the most common subject withdrew because of tolerability. However, of note is combinations in the back and lower limbs (47%) and the neck the fact that they were paid US$25/h upon completion of and upper limbs (29%). The prevalence of chronic pain with the trials. NC was also higher in women (60%), and those living in rural Caution is advised in prescribing cannabis especially in areas, and peaked at ages 50–64 years. There was no young patients, due to increased psychosis after long-term use. reference to pain intensity in these profiles. The challenge may be to identify individuals for whom this Due to the involvement of multiple pain sites in chronic treatment can used safely, to effectively target the therapeutic pain with NC, the authors express concern for the presence of window (lowest effective dose), and to use cannabis with mixed pain syndromes involving distinct mechanisms. other appropriate drugs in an extension of the polypharmacy This is clinically important as multiple medications and approach already in use. treatment modalities may be required for effective control in 1. Abrams DI, Jay CA, Shade SB et al. Cannabis in painful HIV-associated sensory neuropathy: a these circumstances. randomized placebo-controlled trial. Neurology 2007;68:515–21. 1. Torrance N, Smith BH, Bennett MI et al. The epidemiology of chronic pain of predominantly 2. Rog DJ, Nurmikko TJ, Friede T et al. Randomized, controlled trial of cannabis-based medicine neuropathic origin. Results from a general population survey. J Pain 2006;7:281–9. in central pain in multiple sclerosis. Neurology 2005;65:812–9. Address for reprints: D Bouhassira, INSERM U-792, Centre de Traitement Address for reprints: BL Wilsey, Pain Academic Office, UC Davis Medical et d’Evaluation de la Douleur, CHU Ambroise Paré, 9, Avenue Charles de Center, 3020 Ellison Ambulatory Care Center, 4860 Y Street, Sacramento, Gaulle, Boulogne-Billancourt F-92100, France. CA 95817, USA. Email: [email protected] Email: [email protected]
Prevalence of chronic pain with neuropathic characteristics in the general population CHRONIC PAIN Bouhassira D, Lantéri-Minet M, Attal N et al. Pain 2008;136:380–7. A 50 year old man with chronic back pain In this article, the authors report the results of a postal Rathmell JP. survey in France, conducted to identify the prevalence, JAMA 2008;299:2066–77. epidemiology, and likely clinical settings for chronic pain with or without neuropathic characteristics (NC). The In this report, the author describes the case of a 50-year-old results showed that a higher prevalence of chronic pain man with chronic low back pain. The epidemiology and with NC is associated with the age range 50–64 years, potential etiologies of this syndrome, methods for rural areas, and manual professions. differential diagnosis, and best practices for treatment are discussed. There is increasing recognition of the significance of undiagnosed and inadequately treated chronic pain both in Low back pain (LBP) is highly prevalent in the US and is the medical care settings and in the general population. In among the most frequent reasons for both medical care
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utilization and disability. LBP, or lumbosacral pain, is located and interventional pain therapies, there is a lack of information in the lumbar and sacral spinal regions. Common causes of on behavioral therapies for LBP. LBP are early degenerative changes in the spine (including Address for reprints: JP Rathmell, Center for Pain Medicine, herniated nucleus pulposus and internal disk disruption) and Massachusetts General Hospital, 15 Parkman Street, WACC 333, advanced degenerative changes (including facet Boston, MA 02114, USA. Email: [email protected] hypertrophy and spinal stenosis). When pain is accompanied by bladder, bowel, or neurological symptoms, compressive The impact of chronic pain in children and lesions must be ruled out as the source. Evaluation and adolescents: development and initial validation of treatment of LBP includes assessment of the following a child and parent version of the Pain Experience pain types: Questionnaire Hermann C, Hohmeister J, Zohsel K et al. • Acute radicular (leg) pain due to a herniated nucleus Pain 2008;135:251–61. pulposus may be effectively treated with oral analgesics, epidural steroid injections, and lumbar diskectomy when The authors of this report developed and evaluated the Pain pain is persistent. Experience Questionnaire (PEQ) to assess the psychological • Chronic radicular pain due to spinal nerve compression impact of chronic pain in children and adolescents. This may improve after treatment with neuropathic pain psychometric evaluation was based on a sample of children medications or spinal cord stimulation. and adolescents with chronic pain within the German • Acute lumbosacral pain has multiple traumatic causes. population. Factor analysis confirmed the subscales pain Treatment with oral analgesics followed by a course of severity, pain-related interference, affective distress, and physical therapy for persistent pain may be beneficial. perceived social support in the child PEQ, while the parent • Chronic lumbosacral pain has numerous etiologies, version of PEQ contains the subscales interference, severity including failed back surgery syndrome. of child’s pain, and parental affective distress.
In the current case, a 50 year-old-man presents with acute The authors of this report developed and evaluated the Pain radicular pain following disk herniation, which progressively Experience Questionnaire (PEQ) to assess the psychological worsens following diskectomy. His presentation suggests impact of chronic pain in children and adolescents. This chronic lumbosacral pain and radicular pain. There are mixed psychometric evaluation was based on a sample of children results regarding the utility of diagnostic imaging and and adolescents with chronic pain within the German treatment approaches for this pain syndrome. An initial trial population. Factor analysis confirmed the subscales pain with nerve blocks to the facet joints followed by severity, pain-related interference, affective distress, and radiofrequency may be warranted, but was not helpful in this perceived social support in the child PEQ, while the parent patient’s case. For persistent pain, multidisciplinary pain version of PEQ contains the subscales interference, severity of treatment, cognitive–behavioral therapy, or intradiskal child’s pain, and parental affective distress. electrothermal therapy should be considered, and neuropathic Although the need for appropriate pain assessment in pain may be relieved by tricyclic antidepressants, selective the pediatric population has been widely recognized, the norepinephrine reuptake inhibitors, and antiepileptic agents. In pool of psychometric instruments available for those with carefully selected patients with chronic lumbosacral pain, long- chronic pain is very limited. As the authors noted, no term opioid therapy with short- and long-acting agents, alone multidimensional questionnaire for assessing the impact of or in combination with ibuprofen or acetaminophen, and chronic pain in both children and adolescents existed and rapid-onset opioids for breakthrough pain may reduce pain they therefore developed the Pain Experience Questionnaire and improve function. The patient’s current medications are (PEQ) – child and parent versions – to fill this void. clonazepam 1 mg three times daily; cyclobenzaprine 10 mg The child version of the PEQ (PEQ-C) was developed orally three times daily; methadone 40 mg in the morning, based on part A of the German version of the 30 mg at noon, and 40 mg at night; naproxen 500 mg twice Multidimensional Pain Inventory for adults [1]. The parent daily; and oxycodone/acetaminophen 5 mg/325 mg four version of the PEQ (PEQ-P) was developed as a counterpart of times daily, as required. Spinal cord stimulation or intraspinal the PEQ-C with the primary goal of obtaining parental ratings therapy, and lifestyle modification may be considered to of pain severity and interference. In addition, PEQ-P contains decrease pain-related disability. the subscale parental affective distress to assess the parent’s Although this well-written and comprehensive case report mood, irritability, and coping efficacy. A preliminary version of includes much information on the efficacy of pharmacological PEQ was given to a sample of 111 German children and
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adolescents (7–18 years) with chronic pain, and their parents. • Injury of bone and soft tissue and visceral pain disorders Validity analyses were also performed to evaluate age and (n=65) – assuming self-sustaining central gender effects, and the relationships between measures of hyperexcitability, as there were no signs of inflammation emotional well-being, behavioral problems, pain activity, and or peripheral nerve lesions. pain-related cognition. External validity was tested by assessing the patient status (participants in experimental or treatment Patients were randomized to receive either sham or real, studies, inpatients, outpatients). PEQ-C assessed pain severity, high-frequency TENS. Electrodes were applied over the pain-related interference, affective distress, and perceived superficial cutaneous nerves in the painful area(s). After social support, while PEQ-P assessed severity of child’s pain, instruction and baseline evaluation, patients left the outpatient interference, and parental affective distress. clinic and then returned after 10 days. Two outcome measures The results of statistical analyses showed satisfactory were used to predict result of TENS treatment: psychometric properties and indicated that PEQ is a promising tool for a comprehensive assessment of pediatric • The proportion of patients satisfied with the initial pain, although additional validation is necessary. treatment result and who were willing to continue 1. Kerns RD, Turk DC, Rudy TE. The West Haven-Yale Multidimensional Pain Inventory treatment (yes or no). (WHYMPI). Pain 1985;23:345–56. • Pain intensity as measured by Visual Analogue Scale Address for reprints: C Hermann, Department of Clinical and Cognitive scores, which were obtained at the same time every day Neuroscience, Ruprecht-Karls-University Heidelberg, Central Institute of Mental Health, Square J5, D-68159, Mannheim, Germany. for 14 consecutive days. Email: [email protected] or [email protected] To assess psychological factors, cognitive coping strategies Predicting outcome of TENS in chronic pain: a were evaluated using the Pain Coping Inventory (PCI), pain prospective, randomized, placebo controlled trial cognition was measured with the Pain Cognition List, Oosterhof J, Samwel HJ, de Boo TM et al. depression was measured with the Beck Depression Inventory, Pain 2008;136:11–20. and perceived control over pain was measured by answering the question, “Can you decrease the severity of your pain by performing activities distracting from pain, relaxation exercises, This randomized, sham-controlled trial involving patients reducing activities or resting, or none of those possibilities?” with chronic non-cancer pain was to determine the Treatment modality or interactions with treatment effects of the origin of pain, mood, and cognitive modality did not predict intensity of pain. Instead, pain coping strategies on predicting short-term results of high- intensity was predicted by the PCI subscale of resting frequency transcutaneous electrical nerve stimulation (negative relation) and pain disability score (positive (TENS) in the treatment of chronic pain. Main outcome relation). Independent of treatment modality (sham vs. real measures included pain intensity and satisfaction with TENS), baseline variations in pain intensity positively pain. Results showed that treatment modality (real TENS, influenced patients’ satisfaction with treatment results and sham TENS) did not predict pain intensity. Instead, pain increased pain variation was associated with a greater intensity was predicted by resting (negative relation) and chance of successful treatment. In a subgroup of patients pain disability scores (positive relation). with chronic pain due to injury of bone and soft tissue, the Transcutaneous electrical nerve stimulation (TENS) is an easy proportion of patients satisfied with treatment was to use, non-invasive analgesic intervention. The objective of significantly higher in the group receiving real TENS as this randomized, sham-controlled study was to determine compared with those receiving sham treatment. the effects of the origin of pain, mood, and cognitive coping As noted by the authors, the most striking fact is that strategies on predicting short-term results of high-frequency predictors for pain intensity differ from those for patients’ TENS in the treatment of chronic pain. satisfaction with treatment. Although closely related, these two The trial consisted of 163 participants with chronic non- outcome measures differ perhaps because a patient’s cancer pain. Based on medical causes of pain, patients satisfaction comprises considerations of the relevancy of belonged to one of the following pain-diagnosis groups: improvement for the patient, whereas VAS scores reflect a measure of pain intensity perceived at a fixed time. • Osteoarthritis and related disorders (n=57) – assuming Address for reprints: J Oosterhof, Pain Expertise Centre, Department of peripheral sensitization by neurogenic inflammation. Anesthesiology, Radboud University Nijmegen Medical Centre, Geert • Peripheral neuropathic pain (n=41) – as a result of lesions Grooteplein 10, PO Box 9101, 6500 HB Nijmegen, The Netherlands. in the peripheral nervous system. Email: [email protected]
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Childhood chronic recurrent multifocal patient with kyphosis who received PAM therapy, an osteomyelitis: pamidronate therapy improvement of 20° was observed. Bone mass density decreases pain and improves z-scores improved for all sites in those patients treated with vertebral shape PAM for >6 months. The medication did not have any Gleeson H, Wiltshire E, Briody J et al. significant short or medium-term side effects. J Rheumatol 2008;35:707–12. In summary, PAM therapy demonstrated symptomatic benefits in all patients but one. Benefits included improved This retrospective, observational study evaluated vertebral shape and decreased kyphotic angle. However, radiological features in seven pediatric CRMO patients benefits in non-vertebral disease are unclear, with no evidence following pamidronate administration. Chart reviews of radiological improvement in patients with appendicular indicated symptomatic improvement in six patients, and disease or patients with synovial joint involvement. statistically significant improvements in vertebral shape Although the investigators suggest early initiation of PAM and kyphotic angle in three patients at 3-year follow-up. therapy for patients with CRMO, with a short course of If findings are replicated with tolerable side effects, 3–6 months, this small case study is limited in scope and a CRMO patients may benefit from a brief 3- to 6-month controlled trial may be warranted. Patients who present with course of bisphosphonate therapy early on post-diagnosis. reduced bone mass or vertebral fractures may benefit from a longer course. Chronic recurrent multifocal osteomyelitis (CRMO) is an 1. Corrado A, Santoro N, Cantatore FP. Extra-skeletal effects of bisphosphonates. Joint Bone Spine 2007;74:32–8. inflammatory bone syndrome that occurs in children and adolescents. The sequelae include bone lesions, and Address for reprints: C Munns, Institute of Endocrinology and Diabetes, symptoms include mild-to-moderate bone pain. There is The Children’s Hospital at Westmead, Sydney, NSW 2145, Australia. Email: [email protected] currently no cure for CRMO but controlling the inflammation is critical to alleviating its symptoms. Therefore, nonsteroidal anti-inflammatory drugs are usually the first-line treatment. BREAKTHROUGH PAIN Previous data has suggested benefits of bisphosphonate therapy in CRMO patients. Bisphosphonates have been shown to be potent inhibitors of osteoclastic bone resorption An observational study of oncology patients’ with both anti-inflammatory and pain-modifying effects [1]. utilization of breakthrough pain medication The inhibiting quality makes these compounds a logical Davies AN, Vriens J, Kennett A et al. choice in CRMO therapy. Histological evidence shows J Pain Symptom Manage 2008;35:406–11. increased bone turnover in the lesions of CRMO patients, and treatment with the bisphosphonate pamidronate (PAM) In this study, the investigators aimed to identify strategies has been associated with the reduction of this bone turnover. to help improve the management of breakthrough pain In this retrospective, observational study, seven pediatric in community dwelling oncology patients. Data were cases were reviewed to assess the clinical and radiological collected by means of an interview format. The results effects of intravenous PAM therapy. Results from radiological confirmed that most patients do not take breakthrough examinations showed that: pain medication upon every occurrence of such pain.
• All patients had appendicular skeletal involvement This study included 120 oncology patients, all of whom (median four affected sites). were receiving opioids for background pain and 109 of • Five patients had vertebral involvement. whom were prescribed a strong opioid as breakthrough pain • Skeletal features, including kyphoscoliosis and vertebral medicine. Of 87 subjects who experienced breakthrough compression fractures were present. pain, 81 were prescribed breakthrough medicine. Only 15 of the 81 patients used the opioid every time pain was PAM therapy was used for a median of 12 months. At experienced, with another 63 reporting occasional use, 6 months, six of the patients reported decreased bone pain. mainly because the pain was “not always intense/severe”. One patient who experienced no pain relief had synovial Other reasons for occasional use were concerns about or joint involvement. Vertebral morphometry was carried out in experience of side effects, tolerance, addiction, or overdose. three patients and showed improvement in posterior height In addition to the lack of intensity of pain, the authors ratio, middle height ratio, anterior height ratio, and noted that the patients did not take breakthough concavity index during the course of treatment. In one medication every time because of improvement in pain
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before the drug started to work (in three of the 63 Results from the questionnaires administered by the patients). This was likely due to the observed slow onset of team showed improvements in symptom scores by the action of oral opioids, 20–30 min for onset and 60–90 min third day after consultation, most prominently in scores for for peak action. The authors postulate that using an pain, nausea, and dyspnea. Consult recommendations alternative route for administration of opioids, for example including “do-not-resusitate/intubate” and new treatment using oral transmucosal fentanyl citrate, may be of benefit protocol orders were implemented in 88% of cases. In in overcoming this problem. terms of the costs associated with treatment decisions, a Emphasis is placed on the need for improved patient saving of US$107/day for palliative care patients compared education in order to alleviate the concerns about treatment with controls without palliative care consultation was with opioids, and also on improved physician attention to reported. However, there was no significant difference in adverse effects. the overall costs for the entire hospitalization. In a The authors reiterate that the pharmacokinetic profile retrospective analysis of a subset of patients who had died (of the breakthrough opioids used) was clearly unsuitable for in hospital towards the end of the study, the daily cost the temporal characteristics of such breakthrough pain and saving with palliative care consultation was most state that oral transmucosal fentanyl citrate has been shown prominent in the last week of life. to be a more effective and better-tolerated choice for the Methodological problems were acknowledged and management of such pain. included the absence of a control group for symptom analysis and the self-selection bias for inclusion, as Address for reprints: AN Davies, Department of Palliative Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK. 91 (23%) of the initial 395 patients identified chose not Email: [email protected] to participate. Significantly, as the proportion of total hospital stay affected by palliative care intervention increased, the daily PALLIATIVE CARE cost savings increased progressively. This suggests the need to intensify the consultative model to create increased cost savings. Inclusion of some aspects of case management may Clinical and economic impact of palliative also help to achieve this goal. Overall, the challenge may be care consultation to focus on the positive image of the new consultant as a Hanson LC, Usher B, Spragens L et al. positive contributor to well-being rather than the negative J Pain Symptom Manage 2008;35:340–6. perception of the consultant being a care limiter.
Address for reprints: LC Hanson, Division of Geriatric Medicine, This is a prospective observational study of the consultative CB 7550, 258 MacNider, University of North Carolina, Chapel Hill, model of palliative care in an acute hospital. This consultation NC 27599-7550, USA. Email: [email protected] model was shown to reduce the severity of pain, nausea, and dyspnea. Furthermore, when compared with patients A 21-year-old man with chronic pancreatitis matched for diagnosis and mortality risk, palliative care Callery MP, Freedman SD. patients had lower variable hospital costs per day. JAMA 2008;299:1588–94.
Palliative care service, which usually includes consultation The authors of this case summary describe a 21-year-old from an interdisciplinary team, is the most common model man with a long history of chronic idiopathic pancreatitis. of hospital-based services in the US. Over a 3-year period, Results of diagnostic imaging using endoscopic retrograde the authors investigated the impact of such a service on the cholangio pancreatography confirmed the presence of symptoms, treatment, and hospital costs of 304 patients pancreatic duct stones. Endoscopic therapy and specific who were referred to the palliative care team. health behaviors of the patient were the most effective Consultation was provided by part-time physicians, who approaches to reducing his episodic recurrent abdominal were reimbursed by consultation fees, and a full-time- pain and other symptoms of this syndrome. salaried nurse. Each saw the patients on a daily basis. Social workers or chaplains also participated in the study when Currently, there is lack of information on the diagnosis, required. This consultative model is recommendation based, course, and treatment of chronic pancreatitis. In this article, in contrast to the comprehensive model that assumes the case of a 21-year-old man suffering from chronic primary care responsibility and has been shown to reduce pancreatitis characterized by recurrent abdominal pain with costs and resource use. onset during childhood is presented.
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The optimal method for diagnosis of chronic pancreatitis intervention. This suggests that symptoms are potentially is a comprehensive clinical assessment including taking mediated through a neural-based mechanism, independent the patient’s history and reviewing laboratory data. of the pancreas. Computerized tomography or magnetic resonance imaging is Address for reprints: SD Freedman, Beth Israel Deaconess Medical useful for diagnosis, but if imaging results are inconclusive, Center, Dana 501, 330 Brookline Avenue, Boston, MA 02215, USA. endoscopic retrograde cholangio pancreatography (ERCP) Email: [email protected] should be carried out. In this patient’s case, ERCP results indicated chronic pancreatitis with pancreatic duct strictures, Managing an acute pain crisis in a patient papillary stenosis, and duct stones. with advanced cancer: “this is as much of The predominant symptoms of chronic pancreatitis are a crisis as a code” chronic or episodic abdominal pain and nausea. This syndrome Moryl N, Coyle N, Foley KM. may be classified as early or late onset. Early-onset disease is JAMA 2008; 299:1457–67. characterized by a decrease in pancreatic function and development of diabetes mellitus over a lengthy time period. Pain crisis can be defined as the distress of patient and Such a course is unlikely with late-onset disease. Furthermore, family in the experience of severe, uncontrolled pain and it pain is more severe in early versus late onset of disease. requires effective and urgent management while fully The etiology of chronic and acute pancreatitis includes addressing psychological, social, existential, and spiritual both structural and nonstructural causes. Structural causes needs. This detailed case study provides a poignant involve pancreatic duct obstruction, whereas nonstructural example of palliative care needs and institutional resources causes involve metabolic disorders, infections, or genetic for effective acute pain management. Emphasis is placed mutations. Two genes have been implicated in the on the need for urgent consultation by experienced pain pathogenesis of chronic pancreatitis. The protease serine 1 management physicians with immediate attention to pain (PRSS-1) gene is responsible for hereditary pancreatitis and control concurrent with diagnostic evaluation is usually present in adolescents with acute pancreatitis, which progresses to a chronic condition. The cystic fibrosis A pain diagnosis begins with a careful review of recent transmembrane conductance regulator (CFTR) gene is and past history along with a detailed physical examination strongly associated with acute and chronic pancreatitis. that gives direction to the required diagnostic studies. The patient was diagnosed with pancreatitis at the age In addition to the required information about the patient, of 10 years and at that time experienced attacks requiring history is also obtained from the patient’s family as this hospitalizations lasting up to 10 days. During high school, is needed to give focus to the decision process and goals his attacks occurred twice per year, and at 21 years, they for therapy. occur once per year with small intermittent attacks that do The authors of this case study describe a 33-year-old not require hospitalization. Although reducing his fat intake male patient who had advanced metastatic mucinous did not alleviate pain, alcohol abstinence was beneficial. adenocarcinoma of the appendix, developed severe The only medication taken was pancreatic enzymes before abdominal pain, and was thought to be in acute pain crisis. meals. No malaise was experienced and the patient was Despite likely imminent death, full institutional resources active and functional between attacks. The physicians were urgently deployed along with intensive opioid therapy. believed that his condition was improving and perceived Detailed reference is made to the selection of adjunctive that his pain would eventually resolve. Surgical procedures agents used in high doses along with opioids, the concern (e.g. cholecystectomy) were not recommended at that time for opioid complications, and the need for equianalgesic as they could complicate his existing condition. dosing when changing high-dose opioids. This highlights Treatment is directed towards alleviating the the need for clinical pathways to reassure physicians who predominant symptom of the disease – pain. High doses of are attempting to use appropriate intensive care and the pancreatic enzymes (trypsin) improve both pain and need to avoid strategies that may approach euthanasia. steatorrhea. In this case, pancreatic duct obstructions were Interestingly, in this well-recognized center of excellence found to be a contributing factor to the patient’s symptoms for cancer care with frequent pain and palliative care and therefore, removal of such obstructions may be useful consultation (approximately 120/month), only after the in alleviating symptoms of chronic pancreatitis. Other patient was identified as dying and the goals of care were surgical options are recommended only as needed, e.g. if directed towards comfort did the palliative care team inflammation affects proximal structures. Patients have become actively involved. Perhaps clinical pathways can reported that pain often continues despite surgical help to mobilize these resources earlier, in keeping with the
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current concepts of palliative care. This would ensure a tested using hindpaw withdrawal responses elicited by comprehensive, ongoing assessment of medical and patient stimulation with von Frey filaments. and family needs, providing them with support in a holistic BPA was shown to produce a neuropathic pain-like or integrative care model. behavior and long-lasting mechanical hypernociception in the mice that received the real BPA but not those that Address for reprints: KM Foley, Weill Medical College of Cornell University, and Department of Neurology, Pain and Palliative Care underwent sham surgery. Mechanical hypernociception was Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, prevented by local, systemic, or intrathecal administration of New York, NY 10021, USA. Email: [email protected] each of the four antibodies at the time of surgery. In addition, the anti-BDNF was the only antibody that substantially reversed the hypernociception when given ANIMAL MODELS intrathecally or intraventricularly 4 days following the BPA. These findings indicate that NGF, NT-3, and GDNF may have major roles in the onset of the hypernociceptive The role of neurotrophic factors in genesis and alterations in the BPA model, whereas BDNF appears to be maintenance of mechanical hypernociception involved in the maintenance of hypernociception. after brachial plexus avulsion in mice Consequently, NTFs may represent a very interesting target Quintão NL, Santos AR, Campos MM et al. in the therapy for chronic neuropathic pain. Pain 2008;136:125–33. Address for reprints: JB Calixto, Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, 88049–900 Florianópolis, SC, Brazil. Email: [email protected] or The authors of this study evaluated the possible [email protected] involvement of nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic Spread of excitation across modality borders factor, and neurotrophin-3 in the genesis and in spinal dorsal horn of neuropathic rats maintenance of neuropathic hypernociceptive alterations Schoffnegger D, Ruscheweyh R, Sandkühler J. following brachial plexus avulsion in mice. The results Pain 2008;135:300–10. showed that antibodies against these four neurotrophic factors (NTFs) were effective in slowing down the This study involved the use of Ca2+ imaging in spinal development of mechanical hypernociception when cord slices of neuropathic rats to determine whether applied locally, systemically, or intrathecally at the time excitation evoked in deep dorsal horn neurons (which of surgery. These findings corroborate the notion that process non-nociceptive information) leads to neuronal NTF blockers may represent a new class of potential activation in the superficial dorsal horn areas (which targets in neuropathic pain therapy. normally process nociceptive input). The investigators found that in these rats excitation spreads across Neurotrophic factors (NTFs) are proteins that promote both modality borders, mediated by glutamatergic synapses. survival and growth of motor and sensory neurons, and This phenomenon may be a spinal mechanism of regulate neurotransmitter release, long-term potentiation, and mecanical allodynia. synaptic plasticity. NTFs have recently emerged as the novel class of potential targets for development of new drugs for Under physiological conditions, sensory modalities are the management of neuropathic pain. The authors aimed to associated with sensory input to certain layers (lamina) of evaluate the role of nerve growth factor (NGF), glial cell line- the dorsal horn of the spinal cord. Primary afferent Aδ- and derived neurotrophic factor (GDNF), brain-derived C-fibers that mainly transmit nociceptive impulses terminate neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) in the in the superficial dorsal horn in the lamina I/II, whereas genesis and maintenance of the long-lasting neuropathic Aβ-fibers that transmit non-nociceptive impulses terminate hypernociceptive alterations that occur as a result of brachial in deeper laminas (III/IV). Normally, inputs from different plexus avulsion (BPA) n mice. modalities are kept separate to prevent cross-talk between This study involved female Swiss mice undergoing either sensory channels, which would lead to pathological the real BPA or sham surgery only. The mice were treated phenomena such as allodynia. with anti-NGF, anti-GDNF, anti-BDNF, and anti-NT-3T Previous findings in animal models of neuropathic pain antibodies to assess the involvement of NTFs in the onset of indicate that mechanosensitive fibers (projecting to lamina mechanical hypernociception. The hypernociception was III/IV) play a major role in allodynia by activating
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nociceptive-specific neurons in lamina I/II. Peripheral nerve mechanical and thermal stimuli is associated with changes injury is believed to trigger Aβ-fibers to sprout from their in both injured and surrounding uninjured primary neurons normal termination site (found deep in the dorsal horn) and [1]. Plasticity following nerve injury not only induces central to establish synapse-like structures with nociceptive neurons sensitization mechanisms but also alters analgesic drug in superficial lamina I/II. The objective of this study was to efficacy. For example, gabapentin exhibits low efficacy determine whether Aβ-fiber-mediated input may gain access against acute noxious stimuli, but is effective in relieving from lamina III into the superficial dorsal horn, and if so, neuropathic pain and hypersensitivity following nerve which spinal cord membrane receptors are involved in injury. The authors previously showed in an animal model that process. that peripheral nerve injury results in sprouting of spinal Neuropathic condition was induced in male noradrenergic fibers, which may be responsible for a shift in Sprague–Dawley rats using the spared-nerve injury model. drug efficacy [2]. Spinal noradrenergic fibers express Transversal spinal cord slices of neuropathic and control rats troponin receptor kinase B and respond to brain-derived were monitored using Ca2+ imaging to investigate the spread neurotrophic factor (BDNF). In the present study, the of excitation from the deep to the superficial dorsal horn. authors focused on quantifying the effects of peripheral The results demonstrated a violation of modality borders in nerve injury on dorsal root ganglion and spinal cord content the spinal cord dorsal horn of neuropathic but not control of BDNF in rats, and determining the effect of exogenous animals. Furthermore, the spread of excitation from lamina BDNF on spinal noradrenergic fiber density in the absence III into superficial lamina was mediated by glutamatergic of injury. synapses and may be involved in some forms of Aβ-fiber- In this study, male Sprague–Dawley rats were used. mediated allodynia. The findings also indicated that the Unilateral spinal nerve ligation (SNL) of L5 and L6 spinal superficial dorsal horn network is more prone to nerves was performed. Hypersensitivity to light touch synchronous network activity in neuropathic rats compared following SNL in the ipsilateral paw was confirmed using with the controls, possibly contributing to the phenomena of calibrated von Frey filaments. The results showed that “lancinating” pain. SNL induced sprouting of noradrenergic fibers in the dorsal horn of the lumbar spinal cord, and BDNF content Address for reprints: J Sandkühler, Department of Neurophysiology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, increased in the L4–6 dorsal root ganglia ipsilateral to 1090 Vienna, Austria. Email: [email protected] the injury and in the lumbar spinal cord. However, development of such sprouting was prevented by Brain derived nerve growth factor induces intrathecal infusion of BDNF antiserum. This infusion spinal noradrenergic fiber sprouting and also prevented an increase in analgesic efficacy of enhances clonidine analgesia following intrathecal clonidine, which is typically observed following nerve injury in rats nerve injury. Hayashida K, Clayton BA, Johnson JE et al. In control animals that had not undergone SNL, an Pain 2008;136:348–55. intraspinal injection of BDNF resulted in increased density of noradrenergic spinal fibers, mimicking the sprouting The purpose of this study was to quantify the effect of of spinal adrenergic fibers seen after SNL. peripheral nerve injury on the content of brain-derived In conclusion, BDNF plays a crucial role in the sprouting neurotrophic factor (BDNF) in the dorsal root ganglion of noradrenergic fibers after nerve injury. Interfering with and the spinal cord in rats, and to determine the effect BDNF signaling not only blocks the sprouting, but also of exogenous BDNF on spinal noradrenergic fiber the antihypersensitivity effect of intrathecal clonidine, density in the absence of injury. The results suggesting that noradrenergic fiber sprouting is an demonstrated that increased BDNF synthesis spurs important analgesic property of drugs that activate, the sprouting of spinal noradrenergic fibers following augment, or mimic noradrenergic inhibition, and are peripheral nerve injury, and while in the state of approved for treatment of neuropathic pain. 1. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science neuropathic pain, such sprouting may increase the 2000;288:1765–9. capacity for analgesia from drugs that utilize 2. Ma W, Eisenach JC. Chronic constriction injury of sciatic nerve induces the up- regulation of descending inhibitory noradrenergic innervation to the lumbar dorsal noradrenergic pathways horn of mice. Brain Res 2003;970:110–8.
Neuropathic pain is often accompanied by hyperalgesia Address for reprints: JC Eisenach, Department of Anesthiology and Center for the Pharmacologic Plasticity in the Presence of Pain, Wake and allodynia, and poor response to traditional analgesics. Forrest University School of Medicine, Medical Center Boulevard, A previous study demonstrated that hypersensitivity to Winston–Salem, NC 27157, USA. Email: [email protected]
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Contralateral neuropathic pain following a surgical MISCELLANEOUS model of unilateral nerve injury in rats Arguis MJ, Perez J, Martínez G et al. Reg Anesth Pain Med 2008;33:211–6. Pain, catastrophizing, and depressive symptomatology in eating disorders In this study, contralateral allodynia in an animal model Coughlin JW, Edwards R, Buenaver L et al. of neuropathic pain following unilateral spinal nerve Clin J Pain 2008;24:406–14. ligation developed mechanical and cold allodynia in the ipsilateral paw immediately after surgery, whereas these The authors report a study on the relationship between responses in the contralateral paw were delayed up to 21 symptoms of eating disorders (ED) and pain variables. days. These findings indicate extraterritorial development The particular aim was to investigate depressive of neuropathic signs following nerve injury. symptomatology and catastrophizing in association with pain intensities in women with ED. The results Contralateral pain has been demonstrated in a number of demonstrated a correlation between depression and chronic pain types in humans, such as complex regional pain in ED pain syndrome and idiopathic facial arthromyalgia [1]. This pain is typically associated with neuropathic characteristics Although eating disorders (ED) are psychiatric disorders such as allodynia and hyperalgesia. Pain response in listed in the Diagnostic and Statistical Manual of Mental contralateral areas is less intense and appears later than Disorders, 4th Edition, they also carry the unique and that experienced on the affected side of the body. This immediate threat of multiple-organ damage and even death. study was designed to evaluate the appearance, As it is a complex clinical challenge for medical monitoring chronology, and intensity of contralateral allodynia in an and psychological care and because of the high pain experimental rat model of neuropathic pain induced by threshold reported in the population of patients with ED, unilateral spinal nerve ligation (SNL) of L5 and L6 there has been little recognition of pain and associated spinal nerves. psychological variables. The study was conducted using 30 male Sprague–Dawley This broad-spectrum, correlational study consisted of 492 rats weighing. Sham surgery was performed on seven of the female patients with a range of conditions who were divided rats, while the others underwent real SNL. Mechanical alloynia into five subgroups: ED, migraine, temporo-mandibular was tested using von Frey filaments, whereas cold allodynia disorder, back pain, and healthy controls. was tested by application of a drop of cold liquid onto the The results demonstrated a high prevalence (36%) of plantar side of each paw. moderate or severe pain in ED patients, with a four-fold The results demonstrated that the group of animals that greater prevalence of severe pain compared with the had undergone SNL developed mechanical allodynia that controls. The highest correlation (approximately 50%) was significantly higher than baseline on all days following existed between ED and facial and abdominal pain, whereas SNL (days 1–21) in the ipsilateral paw, whereas it only fewer ED patients (approximately one-third) had leg and became significant in the contralateral paw on day 10 until lower back pain. In the ED group with moderate-to-severe the end of the study. Cold allodynia in the ipsilateral paw pain, nearly two-thirds had Beck Depression Inventory (BDI) was also significantly higher from day 1 after SNL for the scores consistent with major depression, which was double entire duration of the study, whereas cold allodynia in the the rate of those who had mild or absent pain with similar contralatral paw developed later, on day 21. Both BDI scores. After controlling for depressive symptomatology mechanical and cold allodynia in the contralateral paw were in this ED group, pain intensity was less than for those with less intense than in the ipsilateral one. the pain disorders and was similar to the controls. These findings have implications for future studies and Catastrophizing has previously been found to be strongly therapeutic approaches. They showed that in the model of associated with pain conditions [1,2], this was also neuropathic pain, the contralateral side cannot be used as a demonstrated in this study. However, after controlling for control. Furthermore, the results open up a possible way of depressive symptomatology in the ED group, such correlation studying the mechanisms of extraterritorial neuropathic pain. was non-significant, a finding similar to the correlations 1. Milligan ED, Twining C, Chacur M et al. Spinal glia and proinflammatory cytokines between catastrophizing and pain in other populations. mediate mirror-image neuropathic pain in rats. J Neurosci 2003;23:1026–40. Perhaps over-riding the impressive correlational data in Address for reprints: MJ Arguis, Department of Anesthesiology, Hospital this study is the clinical pearl to remain focused on detailed Clinic, Villarroel 170, 08036 Barcelona, Spain. Email: [email protected] and repeated pain assessment in patients with this complex
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psychological and medical disorder. Clinicians may be anti-inflammatory drugs, acetaminophen, and opioids, perhaps distracted by multiple medical needs and patients may have there should be more emphasis on exploring the value of other high pain thresholds, but the exploration and treatment of analgesic agents in multidrug cocktails. Novel uses for pain conditions should have a significant impact on well- neuropathic pain medicines, especially in clinical settings involving being and, more importantly, offer hope for a more mixed pain disorders, is a consideration for further study. receptive care environment and better response to overall Evidence that opioids can induce pain facilitatory as well ED treatment. as pain inhibitory systems needs to inform clinical situations 1. Edwards RR, Bingham CO 3rd, Bathon J et al. Catastrophizing and pain in arthritis, of inadequate pain control and problems of pain control fibromyalgia, and other rheumatic diseases. Arthritis Rheum 2006;55:325–32. 2. Sullivan MJ, Thorn B, Haythornthwaite JA et al. Theoretical perspectives on the relation during dose reduction. In these settings, using various between catastrophizing and pain. Clin J Pain 2001;17:52–64. combination therapies to address multiple mechanisms will Address for reprints: JW Coughlin, The Johns Hopkins School of test the skills of pain managers. Medicine, 600 North Wolfe Street, Meyer 101, Baltimore, MD 21287, Address for reprints: J Filitz, Department of Anesthesiology, University USA. Email: [email protected] Hospital Erlangen, Krankenhausstra‚ e 12, D-91054 Erlangen, Germany. Email: [email protected] Supra-additive effects of tramadol and acetaminophen in a human pain model Individual differences in pain sensitivity: Filitz J, Ihmsen H, Günter W et al. genetic and environmental contributions Pain 2008;136:262–70. Nielsen CS, Stubhaug A, Price DD et al. Pain 2008;136:21–9. In this rigorously designed and executed study, the investigators evaluated the individual and combined In this study, identical and fraternal twins were assessed effects of tramadol and acetaminophen on analgesia to determine the extent to which the same genetic and and antihyperalgesia. Patients underwent electrical environmental factors affect sensitivity to cold-pressor stimulation in order to assess pain intensities and pain (CP) and contact heat pain (HP). The results distinct areas of hyperalgesia. Using pharmacodynamic showed that a substantial proportion of variance in pain modeling, results showed that this combination of sensitivity in humans is genetically mediated, and that opioid and non-opioid produced supra-additive effects CP and HP are distinct phenomena from both a genetic regarding both analgesia and antihyperalgesia. and an environmental standpoint.
The aim of this study was to investigate both the individual Pain sensitivity varies widely between individuals. Findings and combined analgesic and antihyperalgesic properties from animal studies indicate that variations in pain sensitivity of the weak opioid tramadol and the non-opioid are partially mediated by genes. The heritability of human acetaminophen in an experimental pain model in humans. pain sensitivity is less well-understood; thus, there is The authors used an established model of inducing pain uncertainty as to whether genetic factors may have and hyperalgesia using graded electrical pulses to the sufficient impact to be of clinical importance and to warrant forearm. Intravenous doses of the two drugs were large genetic studies. To date, human twin studies of a administered both individually and in combination (with number of chronic pain conditions have demonstrated each being dosed at half strength). heritability, but these findings were inconclusive as pain In this study, the individual analgesic effects of sensitivity and severity of pathology were confounded in acetaminophen and tramadol were found to be similar to clinical conditions. The aim of this investigation was to that of the half-dosed combination in providing significantly estimate the heritability of experimentally induced cold- enhanced efficacy. Acetaminophen alone had significant pressor pain (CP) and contact heat pain (HP), and to whereas tramadol had non-significant antihyperalgesic examine whether heritability is equal across pain modalities. effects; however, the combined therapy, at half doses The population sample consisted of 53 identical and each, showed enhanced antihyperalgesic efficacy. These 39 fraternal twin pairs, as well as four single twins whose results indicate a supra-additive effect for analgesia and co-twins did not participate. This sample of 110 women and hyperalgesia with combined acetaminophen and tramadol. 78 men were aged 23–35 years. Each subject underwent CP Furthermore, as different types of pain are often and HP testing. Computerized visual analogue scales (VAS; experienced simultaneously, there may need to be increased 0–100) were used to rate pain intensity (VAS-I) and focus on the use of combination therapy. Although there is a discomfort (VAS-A), representing the sensory and affective long history of the benefits in combining nonsteroidal dimensions of pain, respectively.
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The results showed that genetic factors accounted for the semantic ambiguity regarding the concepts of 60% variance in CP. In addition, there were significant sex hyperalgesia and allodynia. differences, with women describing more pain than men To illustrate their concern, the authors refer to the following CP stimulation. For HP, the estimated heritability results of a study they performed in patients with was 26%, and there were no significant sex differences. neuropathic pain [1]. In the study, von Frey monofilaments Moderate correlation between genetic and environmental (VFMs) were used to determine a mean pain threshold. factors was observed in both pain modalities. Genetic factors VFMs of varying degrees of stiffness were applied to the affecting both phenotypes explained 7% of variance in CP affected and non-affected skin and patients were asked and 3% of variance in HP. Environmental factors affecting to indicate whether they perceived the VFM stimulus both phenotypes accounted for 5% of variance in CP and as painful or not. Interestingly, the authors found 8% of variance in HP. that although the pain threshold could be determined The results from this study are consistent with findings on the affected skin, none of VFMs were painful on from animal studies showing that a major proportion of the the non-affected skin. As VFMs represented stimuli variance in pain sensitivity is genetically mediated. These that normally were not painful stimulation, the authors findings also indicate that genetic effects are modality therefore measured allodynia not hyperalgesia based on dependent. From both an environmental and a genetic the above-mentioned definitions. However, this is in standpoint, CP and HP appear to be distinct phenomena. contrast to the general opinion in medical literature This notion has important implications for future research. implying that quantitative sensory testing with VFM Particularly, the CP stimulus may be a promising phenotype measures hyperalgesia. for future genetic studies, as it showed substantial In general, to quantify the intensity of stimulus- heritability and consistent gender differences. dependent pain, the pain threshold is determined on affected skin. The pain threshold can be expressed as the Address for reprints: CS Nielsen, Division of Mental Health, Norwegian Institute of Public Health, PO Box 4404, Nydalen, NO-0403 Oslo, intensity of stimulus needed to arouse the patient’s verbal Norway. Email: [email protected] response to pain. In quantifying hyperalgesia, the subjective pain intensity Quantitative sensory testing with von Frey of the stimulus that also induces pain on healthy skin monofilaments in patients with allodynia: should be assessed on Visual Analogue Scale or Numerical what are we quantifying? Rating Scale. This stimulus intensity is not abnormal, rather, Keizer D, Fael D, Wierda JM et al. it is the pain response that is exaggerated. Clin J Pain 2008;24:463–6. To quantify allodynia, the lowest intensity of a non- painful stimulus needed to evoke pain response on the The main purpose of the article is to invite clinicians affected skin, also referred to as pain incidence, can be and researchers to carefully examine the semantics of measured. The advantage is that in using this method, the terms allodynia and hyperalgesia, and to raise a allodynia can be quantified objectively as the subjective discussion on this topic. The authors refer to potential response of the patient is reduced to either yes (it was misinterpretations of results of quantitative sensory painful) or no (it was not painful), while the stimulus testing, and discuss possible ways of measuring intensity (e.g. degrees Celsius for thermal allodynia) and interpreting both allodynia and hyperalgesia. is recorded. The authors suggest that the diagnosis of either Quantitative sensory testing is routinely performed in allodynia or hyperalgesia should be based on the patient’s patients with neuropathic pain to quantify stimulus- report of painful or not painful after stimulation of the dependent pain. Stimulus-dependent pain mainly refers to affected skin, with non-affected skin used as the reference two phenomena, allodynia and hyperalgesia. However, the standard. In addition, although the IASP definition of authors note that the use of the terms “hyperalgesia” and hyperalgesia is the gold standard, the authors argue that “allodynia” is misleading. A widely accepted definition of it is of limited use for quantitative sensory testing in hyperalgesia (International Association for the Study of Pain clinical conditions. [IASP], the Subcommittee on Taxonomy, 1994) is “an 1. Keizer D, van Wijhe M, Post WJ et al. Quantifying allodynia in patients suffering from unilateral neuropathic pain using von Frey monofilaments. Clin J Pain 2007;23:85–90. increased response to a stimulus which is normally painful”, and for allodynia is “pain due to a stimulus that does not Address for reprints: D Keizer, Department of Anesthesiology, normally provoke pain.” The authors raise the question of Pain Management Centre, University Hospital Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. what “normally painful” means, and this article addresses Email: [email protected]
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Post herpetic itching – a treatment dilemma meant that he required peritoneal dialysis. Two months after a Semionov V, Shvartzman P. diagnosis of herpes zoster opthalmicus, he experienced pruritis Clin J Pain 2008;24:366–8. around his left eye and forehead for approximately 1 week, and reported an itching intensity of 10/10, but no pain. Post-herpetic neuralgia (PHN) and post-herpetic itch Initially, he was treated with carbamezepine 200 mg/day and (PHI) are complex conditions that can develop following hydroxyzine 75 mg/day for 3 days, which lead to an an outbreak of herpes zoster. The authors of this article improvement of the pruritus. Due to drowsiness, hydroxyzine describe the case of a 22-year-old man who presented was decreased to 50 mg/day and carbamazepine was with pruritus near the left eye and forehead. After increased to 400 mg/day. This regimen was used for 2 weeks, 2 weeks of treatment with a combination of during which time the pruritus completely cleared up. antihistamine and antiepileptic agents, the patient’s 1. Shmelz M. Complex interactions between pain and itch. Pain 2006;124:9–10. 2. Bueller HA, Bernhard JD, Dubroff LM. Gabapentin treatment for brachioradial pruritus. pruritus was resolved. J Eur Acad Dermatol Venereol 1999;13:227–8. 3. Yesudian PD, Wilson NJ. Efficacy of gabapentin in the management of pruritus of unknown origin. Arch Dermatol 2005;141:1507–9. The etiology and management of post-herpetic neuralgia (PHN) and post-herpetic itch (PHI) are uncertain at Address for reprints: V Seminov, Department of Family Medicine. present. Approximately 20% of patients with herpes zoster Ben-Gurion University of the Negev, PO Box 653, Beer-Sheva 84105, Israel. Email: [email protected] develop PHN, whereas 13% develop PHI. Significant risk factors for PHN include age, ophthalmic zoster, and immunosuppression. PHI may be accompanied by pain and Bee venom acupuncture for musculoskeletal pruritus, which can be severely disabling. A multicenter pain: a review study of existing data on 586 adults with shingles or PHN Lee MS, Pittler MH, Shin BC et al. demonstrated that: J Pain 2008;9:289–97.
• Pruritis usually accompanies acute zoster and PHN. In this systematic review, 11 randomized clinical trials • There is no significant difference in age between patients (RCTs) that examined the benefits of using bee venom with or without PHI. acupuncture (BVA) for the treatment of musculoskeletal • Patients with shingles affecting their head, face, and pain were evaluated. Although the results suggested neck are more likely to experience PHI than those with that BVA was effective, this therapy cannot yet be shingles on their torso. recommended due to the low number of high-quality RCTs conducted to date. The mechanisms of PHN and PHI are believed to be related to the loss of peripheral sensory neurons, which In Eastern and Western countries, bee venom therapy (BVT) could possibly result in: has been used to treat arthritis and chronic inflammation. However, no empirical evaluation of the effectiveness of • Hyperactivity of the hypoafferented central itch- and BVT for various musculoskeletal pain syndromes has been pain-specific neurons. performed to date. Thus, the goal of this systematic review • Selective preservation of peripheral pain- and itch fibers was to summarize and review the evidence from all from unaffected adjacent dermatomes. published articles on randomized clinical trials (RCTs) that • The excitation of second-order sensory neurons. relate to the use of BVT for musculoskeletal pain syndromes and assess its effectiveness. Recent data has shown that proteinase-activated A total of 11 RCTs were evaluated consisting of receptors are linked to both pain and itch, indicating the the following: involvement of similar mechanisms and mediators of neuronal sensitization in the two [1]. • One RCT that compared BV acupuncture (BVA) alone There is no known single best treatment for PHN and PHI with control saline injection. but case reports of relief using gabapentin for the treatment • Three RCTs that compared BVA alone with classic for neuropathic pruritis exist [2,3]. Based on these findings, the acupuncture alone. authors chose to treat their patients with a combination of • Three RCTs that compared BVA and classic acupuncture antihistaminic and antineuropathic pain agents. with classic acupuncture alone. The patient in this case study was a 22-year-old male, with • Four RCTs that compared BVA and classic acupuncture a history of non-Hodgkin’s lymphoma. Chronic renal failure with control saline injection and classic acupuncture.
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Three independent reviewers assessed all RCTs for the should be assessed as placebo controls were recognized as quality of the methodology using the Jadad scoring system being different to the BV injections because of the side (range 0–5) and trial validity using the Oxford Pain Validity effects associated with BV injections. These side effects Scale (OPVS; range 0–16). include itching, pain, or redness at the injection site. The reviewers’ evaluations deduced the following: The current findings show that although BVT may be an effective treatment for musculoskeletal pain, there • The overall quality of the articles on the Jadad scale was is still no definitive conclusion with regard to the overall moderate (mean score 3). effectiveness of BV therapy. These data suggest a need for • Validity scores on the OPVS scale were generally in the trials with larger sample sizes and longer treatment periods range of 6–15. that are double-blinded and that control for placebo effects. • BVA groups exhibited greater pain reduction than control Furthermore, the safety of BVA administration requires groups for all 11 RCTs except one. evaluation due to associated anaphylaxis.
Address for reprints: MS Lee, Complementary Medicine, Peninsula The results of this systematic review show that Medical School, Universities of Exeter and Plymouth, 25 Victoria Park low-quality scores were due to small sample sizes, high Road, Exeter, EX2 4NT, UK. Email: [email protected] or attrition rates, and low number of treatment sessions. [email protected] Studies did not evaluate the success of blinding, which
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Highlights from the American Pain MEETING REPORT Foundation’s Roundtable. Provider Prescribing Patterns and Perceptions: Identifying Solutions to Build Consensus on Opioid Use in Pain Management
Baltimore, MD, USA, November 9, 2007
Micke A Brown, RN, BSN1, and Amanda Crowe, MA, MPH2 1American Pain Foundation, Baltimore, MD, USA; and 2Impact Health Communications, LLC, Darien, CT USA
The American Pain Foundation (APF) is a non-profit patient (Massachusetts General Hospital, Boston, MA, USA) stated advocacy organization dedicated to improving the quality of “The challenge is changing fear to respect for a healthy life for people suffering from pain. APF recently convened a balance between the risks and benefits of these medicines”. roundtable meeting, supported by a grant from Endo He added, “It’s an important time to influence change Pharmaceuticals, to discuss and identify actionable solutions because we are seeing the pendulum swing back in the that will encourage better understanding and use of opioid direction of increasing difficulty to access opioids”. therapy for pain management. This meeting served as a Much of the discussion focused on an assessment of critical first step to promote a national dialogue regarding current provider prescribing patterns and perceptions, as opioids and to begin to break through the persisting barriers well as on the real and perceived barriers to opioid surrounding their therapeutic use. The esteemed panel of prescribing, including the extent to which fears of addiction, experts – all with extensive professional experience on the abuse, diversion, regulatory scrutiny, and legal recourse drive front lines of pain medicine – came to the table with unique clinical decisions. Participants of the discussion asserted that perspectives about how to best develop balanced opioid- in order to successfully adopt the “principle of balance” for related policies, clinical practices, and research to ensure opioid-related clinical and regulatory practices, it is essential appropriate access and safety concerning opioid use. to engage other healthcare providers (e.g. family medicine In his opening statement, Will Rowe, Chief Executive and other medical specialists, nurses, pharmacists, physician Officer of APF (Baltimore, MD, USA), set the stage by assistants) and enlist and collaborate with champions within declaring: “It’s time to advance this [opioid management] the pharmaceutical, managed care, legislative, regulatory, issue from the patient’s perspective, not simply in terms of and law enforcement arenas. recommending opioid therapy, but looking at it in a rational Dr Russell Portenoy (Beth Israel Medical Center, New and clear way, devoid of any zealotry on either side. There York, NY, USA), co-moderator of the roundtable, are clear biases tagged to this issue, and often lost in the commented, “The pain community – the “we” – has neither debate are patients who deserve access to optimal pain care, the manpower nor the skills to do this…[we] must figure out which may include use of these medications”. who and where the local champions are”.
Issuing a call to the pain community Defining the problem The panel sounded an urgent call to the pain community to Alleviating pain remains an important medical imperative. begin to reframe the discussion about opioid therapy in a However, pain remains woefully undertreated due, in part, manner that will incorporate a more balanced perspective of to a lack of training in pain medicine, as well as the the risks and benefits of these medications. Paul Arnstein persisting misconceptions, fears, and stigma surrounding
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MICKE A BROWN AND AMANDA CROWE
pain management, especially the use of opioid analgesics. • Lack of education and training in pain medicine, The limited evidence of long-term safety and effectiveness especially among primary care providers. There is an of opioids for non-cancer pain has also been problematic for urgent need to build a network of physicians who are regulators and some prescribers. However, overriding fears adequately trained and willing to care for patients with must be replaced by a more rational, science-based chronic pain. At present, there is only one pain specialist appreciation of the risks and benefits of these medications. for every 21 000 persons living with pain. There is Panel members also called attention to the shift from illicit anecdotal evidence that non-clinical judgments (e.g. drug use to non-medical uses of prescription drugs, which societal and legal issues) may outweigh clinical has paralleled the rapidly advancing knowledge of the considerations in the decision to prescribe opioids. neurobiology of pain and the increasing use of opioids for • Absence of standards of care for the effective use of legitimate medical purposes. This trend has fueled fears and, opioids for long-term, non-cancer chronic pain for some, blurred the line between the law and the practice management. As a result, under- and overtreatment may of medicine. occur concurrently. The roundtable participants noted that opioid therapy has • Discussions regarding opioid prescribing patterns and been, and continues to be, an emotionally charged, divisive challenges are often limited to the world of pain and issue. They voiced concerns over the tendency for tragic stories academic medicine; the primary care profession and of lives lost to abuse to become headline news and to go to other stakeholders should also be engaged. public hearings, which overshadow daily accounts of the • State, legal, and regulatory barriers interfere with the debilitating and life-limiting effects of untreated or undertreated medical use of opioids for pain relief. Fear of scrutiny by pain. These stories are misleading and fail to balance the needs such bodies and possible action by enforcement agencies of pain patients – very few of whom abuse their medications – has had a “chilling effect” on the willingness of doctors with society’s need to stem medication abuse and diversion. to prescribe adequate doses of opioids for pain Patients with severe, long-term pain require access to strong management. The roundtable group raised concerns pain medications, which may include opioids, to help restore about reports of patients who use opioids for pain their physical functioning and quality of life. management being “fired” from practices that are Key issues discussed by the group included the unwilling to assume the risk of scrutiny, often with no assumptions and ideas that: transition plan in place. • Inadequate reimbursement of pain medications may hinder • Pain is undertreated in America. access due to the impact of formulary restrictions, rising • The chronic pain conversation must broaden in scope. co-payments, and Medicare Part D policies, among other • Pain management must be presented with a more factors. In addition, some pharmacies do not stock opioids. balanced point of view. • Failure to shift focus from a fear-based prescribing • All individuals or groups concerned with pain practice (reactive) to risk management (proactive). The management must work collaboratively. discourse regarding opioids should center on the efficacy of opioids – when they should be appropriately used and Barriers to appropriate opioid prescribing how to manage associated risks. Thought leaders and management recognize that there is a risk in pain management using Roundtable participants identified the following as important opioids, but assert that such risk can be managed barriers to appropriate opioid management: effectively, and that physicians are poised to mitigate this risk. Addictive medicine principles are critical to • Lack of confirmatory data about the long-term safety successful pain management. and efficacy of opioids in non-cancer chronic pain, amid • News media coverage and sensationalized case reports of cumulative clinical evidence. young lives being destroyed because of non-medical access • Persisting stigma and shame, especially surrounding to prescription medications, including opioids. Such reports opioid use and misconceptions that these medications pit one public health problem against another. inevitably lead to addiction. • Limited public awareness and education about all pain Integrating balance at the bedside and beyond relievers (e.g. aspirin, nonsteroidal anti-inflammatory drugs, The group believes that multipronged strategies that aim to opioids) and their safe use. Patients (and providers) also promote a more balanced perspective among key need to be able to better distinguish the phenomena of stakeholders (e.g. healthcare professionals, regulators, law tolerance, physical dependence, and addiction. enforcement, insurance carriers, news media) must be
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HIGHLIGHTS FROM THE AMERICAN PAIN FOUNDATION’S ROUNDTABLE
undertaken to achieve a middle-ground perspective and include complementary approaches such as physical and begin to effect change regarding opioid use in pain cognitive behavior therapies, and interventional strategies, management. Such initiatives should seek to: among others. Studies have increasingly demonstrated that multifaceted pain management plans yield more favorable • Educate healthcare professionals, patients, the news patient outcomes [1–6]. media, elected officials, regulators, third-party payers, and the public about pain management and opioid use. Summary The panel shared the view that there is a need for more There is an urgent need to build a consensus with regard to education and less restriction. “We’re asking people to opioids as safe and effective therapeutic option for do a job they’re not trained to do, and then trying to appropriately selected and monitored patients who suffer give them technical support after the fact”, remarked from chronic pain, while also acknowledging the problem of one panelist. Recommendations included a coordinated prescription drug abuse and diversion. This roundtable effort to integrate pain management training as part of discussion provided valuable insights from some of the the core curriculums at schools of medicine, nursing, and leading pain experts in the US. APF recently released a pharmacy. Engaging and educating the primary care document highlighting the key proceedings and community, which addresses most of the chronic pain in recommendations emerging from this meeting, which may the US, was mentioned, as well as launching a parallel serve as a roadmap for future programming to encourage patient education program. greater collaboration and consensus for opioid therapy and • Develop a collaborative agenda with key members of pain management. To access this report, please visit the APF law enforcement and regulators to bridge the divide and website at: www.painfoundation.org. exchange ideas that may better serve patients and communities. Disclosures • Encourage research trials. As the pain management The authors have no relevant financial relationships to disclose. community continues to move forward, so too must the research that supports specific guidelines and policies References pertaining to pain medicine. Participants of this discussion 1. Cleeland CS, Reyes-Gibby CC, Schall M et al. Rapid improvement in pain management: the Veterans Health Administration and the Institute for Healthcare Improvement called for an aggressive research agenda to generate long- collaborative. Clin J Pain 2003;19:298–305. term studies of the effects of pain management therapies, 2. Dahl JL, Gordon DB, Ward S et al. Institutionalizing pain management: the Post-Operative Pain Management Improvement Project. J Pain 2003;4:361–71. as well as studies that demonstrate the effectiveness of 3. Gordon, DB, Dahl JL, Miaskowski C et al. American Pain Society Recommendations for Improving the Quality of Acute and Cancer Pain Management, American Pain Society different processes such as documentation, opioid rotation, Quality of Care Task Force. Arch Intern Med 2005;165:1574–80. and multimodal therapy. 4. Gordon DB, Pellino TA, Miaskowski C et al. A 10-year review of quality improvement in pain management: recommendations for standardized outcome measures. Pain Manag Nurs 2002;3:116–30. Roundtable participants reiterated the need for 5. Turk DC, Dworkin RH, Allen RR et al. Core outcome domains for chronic pain clinical trials: individualized treatment goals and the expectations for trials IMMPACT recommendations. Pain 2003;106:337–45. 6. Zech DF, Grond S, Lynch J et al. Validation of the World Health Organization Guidelines in opioid therapy. The use of opioids must be integrated into for cancer pain relief: a 10-year prospective study. Pain 1995;63:65–76. comprehensive, multimodal treatment plans that may also
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Forthcoming International Events 2008
OCTOBER NOVEMBER DECEMBER
6 6–8 3–5 SC Pain Management Conference 11th International Conference on the Pain Management for Health Hilton Head Island, SC, USA Mechanisms and Treatment of Plans 2008 Contact: CME Office Neuropathic Pain Las Vegas, NV, USA T +1 803 434 4211 Bermuda Contact: World Research Group F +1 803 434 4288 Contact: CPE Office T +1 800 647 7600 E [email protected] T +1 585 275 4392 F +1 781 939 2543 W http://cme.med.sc.edu F +1 585 275 3721 E [email protected] E [email protected] W www.worldrg.com/pain 18–22 W www.neuropathicpain.org American Society of Anesthesiologists 2008 Annual Meeting 8 Orlando, FL, USA Cornell 2nd Pain Medicine Contact: ASA Symposium: Evidence Based Practice T +1 847 825 5586 & Updates in Pain Medicine F +1 847 825 1692 New York, NY, USA E [email protected] Contact: Marlene Augustine W www2.asahq.org T +1 212 746 2785 F +1 212 746 8563 30 October –1 November E [email protected] 19th Annual Meeting of the W www.cornellpainmedicine.org Alliance of State Pain Initiatives Madison, WI, USA 14–17 Contact: CME Office 1st International Headache Summit P +1 608 265 2760 Tel-Aviv, Israel F +1 608 262 8421 Contact: Elizabeth H Jett E [email protected] T +1 212 794 3550 W www.aspi.wisc.edu F +1 212-794-0591 E [email protected] W www.headache-summit.com
22 14th Annual Pain & Symptom Management Conference 2008 Toronto, ON, Canada Contact: CEPD Office T +1 416 978 2719 F +1 416 946 7028 E [email protected] W www.cme.utoronto.ca
If you would like your meeting listed here, please contact the Senior Editor (for details see inside front cover).
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ADVANCES IN PAIN MANAGEMENT
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