Pharmacology of Pain

Q: Why did you and your coeditors decide to put together a book on the pharmacology of pain?
A: Initially, David Lussier and I came up with the idea because we wanted to fill a gap in the literature. There are many interesting books published by IASP Press, but we thought that a volume dedicated to pain pharmacology was necessary in view of the many recent advances in the field. Indeed, a book series edited by Anthony Dickenson was available in the 1990s, but this field is evolving so rapidly that we were sure that a new book was a priority for the pain community, and indeed for everyone involved with patients in pain. Frank Porreca, as a leading expert in the field of pain pharmacology and also section editor for PAIN, was the perfect person to complete the team. Therefore, the idea of a book offering an overview of current drug treatment for pain was launched.

Q: How does this book differ from other pharmacological texts that cover analgesics and adjuvant medications?
A: Although it is to be expected that most textbooks are written by experts, I have to say that for this particular book we have been able to involve the leading international experts in the field, so that excellence is the first thing that comes into my mind when you ask me how it is different from other books. Second, it is rare to find a book dedicated to the pharmacology of pain. Pain textbooks have a section on pharmacological treatments, but our book is solely dedicated to pain pharmacology, which gives us the necessary depth to be exhaustive on this topic. Another point is the structure of each chapter. Authors have been asked to integrate into their chapter some meaningful clinical data in order to cover both basic and clinical pharmacology. Furthermore, we have dedicated a whole section of the book on clinical pharmacology of pain in specific patient groups. The book also covers special topics such as the pharmacology of tolerance, dependency and addiction, pharmacogenetics, and models of pain.

Q: In what ways has our knowledge of the mechanisms of pain improved in the past few decades?
A: There has been tremendous progress in the understanding of pain mechanisms in that time frame. You only have to look at the number of publications in the field, the number of new pain journals, and the interest of the scientific community. To give a few examples, consider the discovery of the crucial role played by glia in the pathophysiology of pain, the finding of new pain pathways, the demonstration of how descending facilitation and inhibition modulate pain signals, and the recent breakthrough in uncovering the role of the transient receptor potential family of receptors.

Q: Have the options for pain treatment changed significantly over this time frame?
A: Yes, indeed. The number of potential pain targets has increased dramatically, as is illustrated in Part II of the book, which covers 14 different approaches to (or targets in) pain treatment. Furthermore, Andy Dray and Martin Perkins have summarized in their chapter the latest developments in ongoing clinical trials using new analgesics.

Q: Do you think we will see new classes of analgesics emerge in the near future?
A: I hope so, but we have to consider that recent times have been disappointing. Indeed, we are still largely counting on “old” drugs such as acetaminophen, NSAIDs, and opioids to treat most pain syndromes. Analgesic antidepressants and anticonvulsants have been used in the last few years to treat neuropathic pain, but again, these drugs are not really new. Thus, despite a real potential for new avenues in pain treatment, we are still eagerly awaiting new classes of analgesics, knowing that a magic drug does not exist and that multimodal analgesia (the simultaneous use of more than one family of analgesics to increase efficacy and to decrease side effects) is crucial to obtain better results. But to come back to your question, I am certain that new classes of analgesics will emerge, but it will take time.

Q: What about new methods of administering existing agents?
A: This is a critical area to consider because it is important to allow optimal delivery of analgesics and at the same time do it in the most innocuous way. For example, a recent method is the transdermal route of administration, especially for the delivery of opioids (e.g., fentanyl or buprenorphine). More sophisticated methods to increase the absorption of analgesics using a small electric current (iontophoresis) through the skin have also been developed. These methods are encouraging, and others should be investigated.

Q: Reading this book has made me aware of the tremendous complexity of pharmacological targets: the cyclooxygenase pathway, opioid and cannabinoid systems, ion channels, neurotransmitters, cytokines, and other receptors. Is it even possible for any one drug to be effective against pain?
A: The answer is no! Some current drugs such as opioids are effective in a large number of situations, but at the expense of troublesome or even life-threatening side effects. As I have already mentioned, the complexity of pain targets is now obvious, and no one magic bullet with be able to address them all. Multimodal analgesia again comes into play because it can tackle many targets with limited side effects.

Q: Placebo analgesia must always be accounted for in clinical research. Are new findings emerging about its mechanisms?
A: Placebo analgesia, like the rest of the field, has evolved tremendously in the last few years. The mechanisms involved in placebo analgesia are much better understood, thanks to new findings that are presented by Pierre Rainville and Serge Marchand’s team in one of the chapters of the book. This area is fascinating, and it was a real pleasure and very exciting to read the latest on that topic. I cannot resist letting you read some of the conclusions made by the authors in this chapter: “Recent studies suggest that the placebo effect is present in many clinical interventions and that it can be, in some cases, very powerful. We now know that the placebo effect depends on a variety of neurochemical and neurophysiological mechanisms, which are measurable and modifiable. This means that the placebo response must not be seen as an indication of weakness or malingering and should not be used to diagnose psychosomatic illness.”

Q: The book includes a section on specific patient groups, including obstetric patients, older persons, infants and children, and obese patients. What’s your philosophy on tailoring a treatment to the individual patient?
A: We are very pleased to include these sections because they are rarely covered in a book, and also because, as you mentioned, drug treatment must be tailored to the individual patient. This is not a philosophical point: it is becoming hard science! Examples are given in the chapter on “Pharmacogenetics of Pain Inhibition” by Jeff Mogil, as well as in the specific clinical section you mention. Indeed, a child and an elderly person do not have the same pharmacology, and neither does an obese person or a childbearing woman, but these people are seen and managed every day by pain physicians and general practitioners. Thus, data concerning these populations and how to manage them are of great importance.

Q: In making the book so very accessible and useful for pain clinicians you are potentially helping many patients receive the very best pain care. Any final comments?
A: One final comment: writing a book on pharmacology of pain does not mean that other pain treatments are obsolete or uninteresting. On the contrary, I firmly believe that other approaches are crucial (including physical activity) and are not in the shadow of “hard” pharmacology. I will even encourage experts in that field to write a book on these topics, like the latest book published by IASP Press by Kathleen Sluka. Thank you for the opportunity to express myself here.

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Contributing Authors
Preface

Part I Background

1. Applied Pain Neurophysiology
   Serge Marchand
2. Toward a Rational Taxonomy of Analgesic Drugs
   David Lussier and Pierre Beaulieu

Part II Specific Pharmacological Pain Targets

3. Targeting the Cyclooxygenase Pathway
   Pascale Vergne-Salle and Jean-Louis Beneytout
4. Pharmacology and Mechanism of Action of Acetaminophen
   Christophe Mallet and Alain Eschalier
5. Pharmacology of the Opioid System
   Christopher J. Evans, A. Charles, J.C. Marvizon, and Y. Ma
6. Pharmacology of the Cannabinoid System
   Josée Guindon, Pierre Beaulieu, and Andrea G. Hohmann
7. Sodium Channels in Pain Pharmacology
   Theodore R. Cummins and Stephen G. Waxman
8. Potassium and Calcium Channels in Pain Pharmacology
   Sérgio H. Ferreira, Wiliam A. Prado, and Luiz F. Ferrari
9. Toward Deciphering the Respective Roles of Multiple 5-HT Receptors in the Complex Serotonin-Mediated Control of Pain
   Valérie Kayser, Sylvie Bourgoin, Florent Viguier, Benoît Michot, and Michel Hamon
10. Glutamate and GABA Receptors in Pain Transmission
    Ke Ren and Ronald Dubner
11. Dopamine Pathways and Receptors in Nociception and Pain
    Francisco Pellicer, J. Manuel Ortega-Legaspi, Alberto López-Avila, Ulises Coffeen, and Orlando Jaimes
12. Neurotrophic Factors, Neuropeptides, and Nitric Oxide: Therapeutic Targets in Chronic Pain Mechanisms
    Amelia A. Staniland, Jean-Sébastien Walczak, and Stephen B. McMahon
13. Cytokines, Chemokines, and Pain
    Claudia Sommer and Fletcher White
14. Adenosine Triphosphate and Adenosine Receptors and Pain
    Geoffrey Burnstock and Jana Sawynok
15. The Transient Receptor Potential (TRP) Family in Pain and Temperature Sensation
    Gehoon Chung, Sung Jun Jung, and Seog Bae Oh
16. Adrenergic and Cholinergic Targets in Pain Pharmacology
    Ralf Baron and Wilfrid Jänig
17. New Pain Treatments in Late Development
    Andre Dray and Martin N. Perkins

Part III Special Topics in the Pharmacology of Pain

18. Vulnerability to Opioid Tolerance, Dependence, and Addiction: An Individual-Centered Versus Drug-Centered Paradigm Analysis
    Guy Simonnet and Michel Le Moal
19. Pharmacogenetics of Pain Inhibition
    Jeffrey S. Mogil
20. Placebo Analgesia
    Philippe Goffaux, Guillaume Léonard, Serge Marchand, and Pierre Rainville
21. Current Animal Tests and Models of Pain
    Daniel Le Bars, Per T. Hansson, and Léon Plaghki

Part IV Clinical Pharmacology of Pain

22. Pharmacological Considerations for the Obstetric Patient
    John S. McDonald and Wing-Fai Kwan
23. Pharmacological Considerations in Infants and Children
    Stephen C. Brown, Anna Taddio, and Patricia A. McGrath
24. Pharmacological Considerations in Older Patients
    David Lussier and Gisèle Pickering
25. Pharmacological Considerations in Obese Patients and Patients with Renal or Hepatic Failure
    Frédérique Servin
26. Pharmacological Considerations in Palliative Care
    Maxine Grace J. de la Cruz and Eduardo Bruera

Index

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"This is an in-depth look at the pharmacology of pain. It is well organized and coalesces a tremendous amount of information into an understandable and useful format. There are numerous figures sprinkled throughout the text, with several in color. The list of contributing authors is prestigious and provides a diversity of expertise and backgrounds. ... This is a well-written, comprehensive review of pain pharmacology that will be useful both to basic scientists with research interests in pain and to pain specialist clinicians."
Reviewed by Tammy L Burns, PharmD, BCPS, Research Director, The Cardiac Center at Creighton University, Omaha, NE, USA. The Annals of Pharmacotherapy, 2011;45:285.

"All of the chapters are first-class presentations of their topics ... The organization of the book facilitates the reader's comprehension with chapters discussing specific targets for pain relief so that all aspects of a specific pathway or set of receptors or channels are discussed in a coherent fashion. I am not aware of another book devoted to the pharmacology of pain that so thoroughly covers all of the important areas. ... This book is a must read for pain specialists who want to have a grasp of all of the key areas in our discipline."
Reviewed by John D. Loeser, MD, American Pain Society E-News, September 2011

"As one who thought he had a reasonable grasp of the basic pharmacology of analgesics, reviewing this volume was a wake-up call. There seems to have been an explosion in basic science, some of which already impacts on clinical practice, some of which is still in process.

"The opening section includes a chapter on applied pain neurophysiology and a proposal for a new taxonomy of analgesic drugs. The second section includes 15 chapters on specific pharmacological pain targets including cyclooxygenase, opioid, cannabinoid, glutamate and dopamine pathways and systems and the role of various ion channels in pain pharmacology. The third section includes an important chapter analysing vulnerability to opioid tolerance, dependence and addiction, as well as a chapter on the placebo response. The final section deals with pharmacological considerations in obstetrics, paediatrics, geriatrics, in patients with organ failure, and in palliative care.

"The chapters are detailed and well-referenced and there is good use of schematic flow diagrams. The editors and IASP Press are to be congratulated and if you want a cutting-edge review of the pharmacology of pain, then here it is."
Roger Woodruff, MD, International Association of Hospice and Palliative Care Newsletter, April 2010

"This publication by the IASP Press provides readers with an update on the current status of knowledge regarding the pharmacology of pain. … [This] comprehensive review of analgesic mechanisms provides a timely update in the literature, filling a gap that has spanned more than a decade. … The book is divided into four parts. The first section provides a current and concise description of pain neurophysiology. This portion is easy to read and presents a well-balanced review on this topic. The cleverly constructed framework guides readers from the basic mechanisms of peripheral nociception upwards to mechanisms of the central nervous system. The discussion aptly incorporates recent research into this subject, for example, the role of glial cells in pain transmission. … The second and most substantial section of the book offers readers a total of 15 chapters, each dedicated to specific pharmacological pain targets. Some examples include the opioid system, sodium channels, the transient receptor potential family, and the cannabinoid systems. The authors put forth tremendous effort in these chapters to provide concise yet comprehensive summaries of the function of these systems, and they were successful in their undertaking. … The chapter that deals with adrenergic and cholinergic targets provides an excellent review of sympatholytic interventions in patients with neuropathic pain. … Section three provides an appraisal of distinctive topics in the pharmacology of pain, including pharmacogenetics, placebo analgesia, animal models of pain, and vulnerability to opioid tolerance, dependence, and addiction. These chapters are organized well and easy to read, which should appeal to a wide range of readers looking for accessible synopses of recent research in these areas. … The fourth and final section deals with the clinical pharmacology of pain with a focus on specific populations, such as obstetrical, pediatric, or geriatric patients. … This section summarizes the fundamental principles regarding the management of these specific populations and is a suitable resource for the clinician. … Overall, this is a praiseworthy textbook that provides a comprehensive update on molecular mechanisms of pain transmission as well as the actions of present and perhaps future therapeutic agents. Although the text provides content relevant for students and clinicians managing painful conditions, the majority of the text would likely appeal to those more interested in fundamental mechanisms of drug action."
Canadian Journal of Anesthesia 2010;57:796-7. Reviewed by Geoff A. Bellingham, MD

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