PERIPHERAL RECEPTOR TARGETS FOR ANALGESIA PERIPHERAL RECEPTOR TARGETS FOR ANALGESIA NOVEL APPROACHES TO PAIN MANAGEMENT Edited by Brian E. Cairns, RPh, ACPR, PhD Faculty of Pharmaceutical Sciences The University of British Columbia A JOHN WILEY & SONS, INC., PUBLICATION Copyright © 2009 by John Wiley & Sons, Inc. All rights reserved. Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada. 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, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. 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Neither the publisher nor author shall be liable for any loss of profi t or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com. Library of Congress Cataloging-in-Publication Data: Peripheral receptor targets for analgesia : novel approaches to pain treatment / edited by Brian E. Cairns. p. ; cm. Includes index. ISBN 978-0-470-25131-7 (cloth) 1. Nociceptors. 2. Nerves, Peripheral. 3. Analgesia. 4. Analgesics. 5. Pain. I. Cairns, Brian E. [DNLM: 1. Pain–drug therapy. 2. Analgesics–therapeutic use. 3. Drug Delivery Systems. 4. Pain–physiopathology. 5. Receptors, Drug–physiology. WL 704 P4456 2009] QP451.4.P47 2009 616′.0472–dc22 2009009731 Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 CONTENTS FOREWORD by Lars Arendt-Nielsen vii PREFACE ix CONTRIBUTORS xi PART I PERIPHERAL MECHANISM IN CLINICAL PAIN CONDITIONS 1 1. Role of Peripheral Mechanisms in Craniofacial Pain Conditions 3 Barry J. Sessle 2. Role of Peripheral Mechanisms in Spinal Pain Conditions 21 Brian E. Cairns and Pradit Prateepavanich PART II SPECIFIC RECEPTOR TARGETS FOR PERIPHERAL ANALGESICS 41 3. Voltage-Gated Sodium Channels in Peripheral Nociceptive Neurons as Targets for the Treatment of Pain 43 Theodore R. Cummins 4. Potassium Channels 93 Daisuke Nishizawa, Toru Kobayashi, and Kazutaka Ikeda 5. Voltage-Gated Calcium Channels as Targets for the Treatment of Chronic Pain 111 Joseph G. McGivern 6. Adenosine Receptors 137 Jana Sawynok 7. Acid-Sensing Ion Channels and Pain 153 Roxanne Y. Walder, Christopher J. Benson, and Kathleen A. Sluka 8. Vanilloid (TRPV1) and Other Transient Receptor Potential Channels 175 Marcello Trevisani and Arpad Szallasi v vi CONTENTS 9. Glutamate Receptors 215 Brian E. Cairns 10. Serotonin Receptors 243 Malin Ernberg 11. Adrenergic Receptors 275 Antti Pertovaara 12. Cholinergic Receptors and Botulinum Toxin 297 Parisa Gazerani 13. Cannabinoids and Pain Control in the Periphery 325 Jason J. McDougall 14. Opioid Receptors 347 Claudia Herrera Tambeli, Luana Fischer, and Carlos Amilcar Parada 15. Calcitonin Gene-Related Peptide and Substance P 373 Ranjinidevi Ambalavanar and Dean Dessem 16. Role of Somatostatin and Somatostatin Receptors in Pain 397 Ujendra Kumar 17. Cytokines (Tumor Necrosis Factor, Interleukins) and Prostaglandins 419 Per Alstergren 18. Neurotrophic Factors and Pain 455 Peter Svensson PART III DELIVERY SYSTEMS 473 19. Topical and Systemic Drug Delivery Systems for Targeted Therapy 475 Urs O. Häfeli and Amit Kale 20. Gene Therapy for Pain 515 Marina Mata and David J. Fink 21. Topical Analgesics 529 Akhlaq Waheed Hakim and Brian E. Cairns Index 537 FOREWORD Knowledge of pain mechanisms has advanced signifi cantly since Wall and Melzack launched the gate control theory in the late 1960s. Since then, an exponential increase in the number of scientifi c papers on this topic has been seen. This has lead to a signifi cant increase in our understanding of the funda- mental aspects of the pain system and its pharmacology, but unfortunately, this has so far not been refl ected in the number of new pharmacological com- pounds available for the treatment of pain. Aspirin, morphine, and lidocaine are still among the most widely used analgesic drugs. However, in more recent years, other centrally acting drugs (e.g., anticonvulsants, antidepressants), not developed or intended for the management of pain, have found their place in modern polypharmacological treatment regimes. Besides lidocaine, antitumor necrosis factor alpha (TNF - α ) and, to some degree, nonsteroidal anti - infl am- matory drug (NSAID ), compounds targeting peripheral sites for pain relief, have been largely neglected. The present book is therefore an important con- tribution in the process of conceptualizing peripheral sites as possible targets for the development of new pain management treatments. This approach could also potentially reduce the well - known signifi cant adverse effects associated with centrally acting analgesic drugs, such as drowsiness, somnolence, and mental clouding as well as gastrointestinal ulceration that is a problem with chronic use of NSAIDs. Such unintended side effects can signifi cantly impact the quality of life of chronic pain patients. Despite these apparent advantages of local analgesics for the treatment of pain, many results from this approach, for example, topical application of analgesic drugs, are disappointing. One reason for failures of this approach is a lack of appreciation of the peripheral pain transduction mechanisms and the diversity of receptors that may be involved in these mechanisms. This book, by reviewing the role of peripheral receptor mechanisms in the transduction of pain, should provide a framework for the development of rationally designed treatments with locally applied analgesics and promote further basic and clinical studies on potentially interesting peripheral receptor targets. L ars A rendt - N ielsen , D r M ed , P h D Center for Sensory - Motor Interaction Department of Health Science and Technology Aalborg University, Aalborg, Denmark vii PREFACE The main purpose of P eripheral Receptor Targets for Analgesia: Novel Approaches to Pain Management is to bring together in one text much of the diverse body of work on peripheral receptor mechanisms of pain. I hoped, by doing this, to allow the reader to compare work done on various receptor targets to determine which targets might be the most useful to pursue in their own research. Thus, the topics I have chosen for the book should be of interest to health sciences researchers and clinicians (physicians, dentists, pharmacists, nurse practitioners, physiotherapists, and others) as well as researchers in the pharmaceutical industry. Nevertheless, I believe that this book will also be attractive to senior undergraduate and graduate students in the health sciences whose research interests include pain. The book is organized into introductory chapters to provide the reader with a general sense of the importance of peripheral mechanism of pain, followed by select topical chapters focusing on specifi c receptor targets. The book fi nishes with chapters that discuss avenues for selective delivery of analgesic agents. I intend that this book will not only provide interesting reading but also serve as useful reference for those interested in the fi eld of pain research. B rian E. C airns Faculty of Pharmaceutical Sciences The University of British Columbia ix CONTRIBUTORS Per Alstergren, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden Ranjinidevi Ambalavanar, Department of Neural and Pain Sciences and Program in Neuroscience, University of Maryland, Baltimore, MD, USA Lars Arendt - Nielsen, Center for Sensory - Motor Interaction, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark Christopher J. Benson, Department of Internal Medicine, University of Iowa, Iowa City, IO, USA Brian E. Cairns, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada Theodore R. Cummins, Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA Dean Dessem, Department of Neural and Pain Sciences and Program in Neuroscience, University of Maryland, Baltimore, MD, USA Malin Ernberg, Division of Clinical Oral Physiology, Department of Dental Medicine, Karolinska Institutet David J. Fink, Department of Neurology, University of Michigan School of Medicine and VA Ann Arbor Healthcare System, Ann Arbor, MI, USA Luana Fischer, Laboratory of Pain Physiology, Division of Biological Sciences, Department of Physiology, Federal University of Parana Parisa Gazerani, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada, and Center for Sensory - Motor Interaction, Aalborg University, Aalborg, Denmark Urs O. H ä feli, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada Akhlaq Waheed Hakim, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada xi xii CONTRIBUTORS Kazutaka Ikeda, Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, Japan Amit Kale, Faculty of Pharmaceutical Sciences, The University of British Columbia Toru Kobayashi, Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, Japan, and Department of Molecular Neuropathology, Brain Research Institute, Niigata University, Niigata, Japan Ujendra Kumar, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada Marina Mata, Department of Neurology, University of Michigan School of Medicine, and VA Ann Arbor Healthcare System, Ann Arbor, MI, USA Jason J. McDougall, Department of Physiology and Biophysics, University of Calgary, Calgary, AL, Canada Joseph G. McGivern, Amgen Inc., Thousand Oaks, CA, USA Daisuke Nishizawa, Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, Japan Carlos Amilcar Parada, Department of Physiology and Biophysics, Institute of Biological Sciences, University of Campinas, Campinas, SP, Brazil Antti Pertovaara, Biomedicum Helsinki, Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland Pradit Prateepavanich, Department of Rehabilitation Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand Jana Sawynok, Department of Pharmacology, Dalhousie University, Halifax, NS, Canada Kathleen A. Sluka, Graduate Program in Physical Therapy and Rehabilitation Science, Pain Research Program, Neuroscience Graduate Program University of Iowa, Iowa City, IO, USA Barry J. Sessle, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada Peter Svensson, Department of Clinical Oral Physiology, School of Dentistry, University of Aarhus; Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, Aarhus, Denmark; and Orofacial Pain Laboratory, Center for Sensory - Motor Interaction, Aalborg University, Aalborg, Denmark Arpad Szallasi, Monmouth Medical Center, Long Branch, NJ, and Drexel University College of Medicine, Philadelpia, PA, USA Claudia Herrera Tambeli, Department of Physiology, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil CONTRIBUTORS xiii Marcello Trevisani, PharmEste, Ferrara, Italy Roxanne Y. Walder, Graduate Program in Physical Therapy and Rehabilitation Science, Pain Research Program, Neuroscience Graduate Program, University of Iowa, Iowa City, IO, USA
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