Novel Aspects of Pain Management: Opioids and Beyond

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From The New England Journal of Medicine:

The goals of Novel Aspects of Pain Management are to provide historical background and a panoramic view of the chemicals that influence pain and to assess the therapeutic potential of many classes of such agents. The book is addressed to academic and pharmaceutical scientists and clinicians seeking new means of pain control. Most of the chapters are informative; they are generally well written and well referenced and attend to major issues. Individual readers will identify chapters that meet their particular needs.

For me, the chapters with a neurobiologic perspective on each class of drug are the best. Chapter 2 is an excellent review of animal models and could have been used to provide context for the entire book. Methods considered in multiple chapters, such as intrathecal drug delivery, should have been reviewed here. There is also the need to define the various kinds of pain discussed throughout the book. Chapter 9, a stimulating review of the neurobiology of the adrenergic system, covers preclinical and clinical studies, the localization and actions of (alpha)(sub 2) receptors, and neuropharmacologic issues. More information could have been provided on the sympathetic nervous system in relation to (alpha)(sub 2)-receptor regulation. Chapter 17 contains a lucid explanation of the isobolographic method for studying drug interactions in the spinal cord. One of the outcomes of concomitant drug administration is to go "beyond opioids" by reducing the doses of opioid or opiate compounds and the associated side effects, such as the psychotomimetic effects of MK-801, an N-methyl-d-aspartate-receptor antagonist. The discussion of dose-response factors that affect the induction of anesthesia in this region will be particularly useful to readers who are not anesthesiologists. A valuable addition to this chapter would be a discussion of studies of ligand binding or of mRNA that assess the independence of receptor regulation during supra-additive drug interactions in the spinal cord.

The strength of this book is in the individual contributions, but its weakness is the lack of integration and perspective. The editors may have hoped that the goals of the book would be reached by each chapter independently, without the need to state clearly the rationale and strategy of the book as a whole. The editors make no initial, organizing statement about the need to move beyond opioids or about the most important areas for development of novel therapies. Each chapter focuses on a class of drugs used in pain management, but the reader receives no guidance about which drugs other than opioids are the most effective today and which will be the most important targets for future development. For instance, every neurotransmitter system is involved to some extent in nociception in the spinal cord, but what is the rationale for pursuing therapies based on purines and (gamma)-aminobutyric acid (GABA) when these transmitters are so widely present in the forebrain and mediate many functions in addition to pain processing? Nevertheless, a useful circuit diagram is provided for the GABAergic system in chapter 12. Specifically, then, the book should have a representative title, an introduction with an adequate overview, and a chapter on basic neurochemistry and neuropharmacology.

The goals of the book are really to discuss drug therapies for managing nociception in the spinal cord. Novel aspects of pain management that goes beyond opioids could easily include new techniques involving neurosurgery, acupuncture, hypnosis, and rehabilitation. In lieu of a thoughtful introduction, the reader should consider the first three pages of chapter 3, in which Ossipov et al. make the case for pursuing therapies other than opioids and briefly address controversies about the value of opioids for treating neuropathic pain. This discussion could have been greatly expanded to provide an introduction to the entire book. The first chapter should have considered the essential pain states and how each is affected by opioid and opiate compounds. Instead, the book begins with a chapter entitled "Neurophysiology of Acute and Chronic Pain," a lightweight effort to summarize the physiology of pain.

Many of the chapters were written as though the mammalian central nervous system consists only of the midbrain and spinal cord. But pain perception occurs in the forebrain, not in the spinal cord. Moreover, all the transmitters engaged in nociception in the spinal cord are also present in the forebrain, and the receptors of these transmitters are modulated by the same drug regimens that regulate spinal cord activity. Only chapter 14 briefly considers pain regulation in the forebrain in relation to dopaminergic regulation. Although anesthesiology focuses mainly on blocking mechanisms of nociception in the spinal cord, it is misleading to refer to efforts to blunt nociception in this region as managing pain per se. In fact, nociceptive processing is blocked in the spinal cord so that pain processing is not engaged in the forebrain. In short, pain management requires knowledge of how drugs and surgical and psychiatric methods affect pain processing in the forebrain. This book, however, never reaches beyond the spinal cord and midbrain. Rather, an overview of all neurotransmitter systems engaged in nociception could have been provided.

Physicians and others interested in information about blocking nociceptive processing in the spinal cord will find this book worth buying and reading. A wider audience also will find it useful because it considers the full range of transmitter systems with complete references and historical background. The chapters are of reasonable length, and the book moves briskly so that the particular needs of a reader can be easily addressed.

Reviewed by Brent A. Vogt, Ph.D.
Copyright © 2000 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.


"This book should be required reading for students entering the field of pain research, as well as for medical students...The structure of the chapters and the exceptional quality of the writing styles make Novel Aspects of Pain Management a pleasure to read." -Trends in Neurosciences

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