Behind the Book

We asked lead editor Pierre Beaulieu for his thoughts on this exciting and timely topic.
Q: What is the main focus of your own research, and how do you divide your time between research, clinical work, and teaching?
A: My main research interest lies in the pharmacology of cannabinoids in the treatment of pain. More specifically, my attention is focused on the mechanisms of neuropathic pain (in animal models) and on how the endocannabinoid system can be modulated in that condition. As a clinician, I also have great interest in the pharmacology of drugs that can reduce pain in the perioperative period, more specifically local anesthetics and nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to cannabinoids. My time is divided between research activities (40%), mainly in the department of pharmacology, where I have a pain lab; my clinical work as an anesthesiologist (40%); and finally, my teaching activities at the Université de Montréal (20%).
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.