Publications
APS Bulletin • Volume 14, Number 6, Summer 2004
Resource Reviews
John D. Loeser, MD, Department Editor
The Genetics of Pain
Reviewed by Alan R. Light, PhD
Edited by Jeffrey S. Mogil. Progress in Pain Research and Management, Volume 28. Seattle, IASP Press, 2004. Hardbound, 349 pages. ISBN 0-931092-51-5. $78.00, IASP Member Price $59.00.
This volume will be useful for clinical pain management teams as a resource for genetically caused pain disorders and unusual reactions to analgesic drugs that have a genetic basis. It should also prove useful for students, researchers, and clinicians looking for a coherent review of the many advances in the use of genetic and molecular techniques to study pain and analgesia at both the preclinical and clinical level.
The Genetics of Pain is a 16-chapter review volume with 38 authors. This timely volume is divided into three parts, Part I covering the “Genetic Building Blocks of the Pain System” (i.e., what is currently known about the genes and their protein products that make up parts of the pain and analgesia transmission and encoding systems). Part II reviews “Pain Susceptibility Genes” (i.e., which genes and their protein products might be responsible for individual variability in pain and analgesia responses, and for pathologic alterations in pain responses). Part III is titled “Complexities, Opportunities and Worries” and reviews gene-environment interactions, social influences on pain, gene therapy, and lastly, both the positive and negative ethical effects the genetics of pain has and may have in the future. Overall, this volume is edited masterfully by Jeffrey Mogil. The individual chapters are extremely informative and what is more rare in review volumes of this type.
Chapters in Part I cover the use of genetically manipulated mice to study pain mechanisms (Chapter 2 by Malmberg and Zeitz), the use of antisense oligonucleotides to knock down specifically targeted genes to determine their involvement in pain and analgesia mechanisms (Chapter 3 by Lai and Porreca), use of microarrays to determine which genes respond by up-or-down regulation to manipulations that alter pain sensitivity (Chapter 4 by Costigan, Griffin and Woolf), and a consideration of how alternative splicing could contribute to species, strain, and individual differences in sensitivity to opioids (Chapter 5 by Pasternak and Pan).
Part II is more clinically oriented and includes seven chapters covering “Pain Susceptibility Genes.” Chapter 6 by Xu and Wiesenfield-Hallin reviews known differences in pain and analgesic responses in rats. Chapter 7 by Mogil demonstrates the power of mouse genetics and reviews a number of complex pain traits that have been mapped to narrow regions of the genome using quantitative trait locus mapping. Probably two of the most interesting outcomes of this research are that genetic mediation of nociceptive sensitivity is related to analgesic sensitivity. In other words, “mice strains that are sensitive to nociception are resistant to morphine analgesia” and vice versa. The other interesting outcome is that different pain modalities (e.g., mechanical, thermal, chemical, and visceral) seem to be genetically distinct, both as to threshold sensitivity and to analgesic alteration. The mechanisms behind this are at present unknown, but point toward as yet unknown common pathways in transduction or central processing. Chapters 8–10 are “The Heritability of Pain in Humans,” by MacGregor; “Congenital Insensitivity to Pain” by Indo; “Migraine Genetics” by Maagdenberg, Palotie and Ferrari. Chapter 11, “Pharmacogenetics, Pharmacokinetics and Analgesia” by Desmeules, Piguet, Ehret, and Dayer includes a thorough discussion of drug metabolism by the detoxifying p450 cytochrome system, which should be required reading by clinicians and researchers alike. Chapter 12, “The OPRM (Mu-Opioid-Receptor) Gene” by Yu, focuses specifically on polymorphisms in the mu opioid receptor gene, and their functional consequences.
Part III of this volume consists of four chapters. The first two (Chapter 13, “Gene-Environment Interactions Affecting Pain Phenotype” by Mogil, Seltzer, and Devor, and Chapter 14, “Social and Environmental Influences on Pain: Implications for Pain Genetics,”) outline the limitations of viewing biology simply as genes and explore the consequences of gene-environment interactions in animals and humans that lead to some surprising outcomes. For example, robust pain behavior in certain strains of rats can be eliminated by small changes in diet. This, of course, should be a warning to clinicians who fail to consider diet, social interactions, and other lifestyle factors thoroughly when treating patients’ pain. Chapter 15, “Gene Therapy for Pain” by Yeomans and Wilson, summarizes the current technology for using molecular strategies to treat acute and long lasting pain and offers insight into promising new treatments.
The final Chaper, “Ethics and the Genetics of Pain,” by Margaret Somerville, examines both ethically troubling and ethically positive aspects of the implications of research into the genetic basis for pain susceptibility and variability in the response to analgesics. A few of these topics are discussed in detail, and many more are listed as potential problems for the future. This is an exciting and important book that opens new vistas in the world of pain.
Dr. Light is Professor of Anesthesiology at the University of Utah in Salt Lake City.
Reviewer content represents the opinion of the reviewer, not APS.
Please direct your suggestions for future Resource Reviews to John D. Loeser, MD, Department Editor, at jdloeser@u.washington.edu