Publications
APS Bulletin • Volume 17, Number 3, 2007
Resource Reviews
John D. Loeser, MD, Department Editor
Cholecystokinin and Its Antagonists in Pain Management
Reviewed by Bradley K. Taylor, PhD
Gary J. McCleane, Binghamton, NY, Haworth Medical Press, 2006. Hard cover, 189 pages, ISBN 0-789028-92- 1, $29.95
Gary McCleane’s Cholecystokinin and Its Antagonists in Pain Management provides a much-needed comprehensive review on cholecystokinin (CCK). The book expands upon a journal review by McCleane that was published in Current Pharmaceutical Design in January 2004. Both publications summarize the vast preclinical rodent data that inversely links CCK with opioid analgesia, both discuss the clinical trials performed through 2003 (many of which the author has performed himself), and both provide convincing arguments for the use of CCK receptor antagonists (in particular, proglumide) as opioid adjuvants for pain management. Both texts are essential for the basic scientist interested in the mechanisms of CCK antagonist-induced potentiation of opioid analgesia. This book is essential for the clinical scientist interested in bringing to the forefront of pain management a strategy involving coadministration of a CCK antagonist with an opioid analgesic.
This book reproduces all of the material and figures presented in the original journal review. In some places (e.g., the discussion of two papers indicating the safety of CCK antagonist/opioid combinations) the texts are quite redundant. But in general, the book provides a much more comprehensive review of the literature. In the discussion of CCK antagonists for chronic pancreatitis, for example, the journal review cites only six articles while the book covers 25 articles. Also, the reduced space restrictions of a book have allowed McCleane greater freedom to solidify his assertion that the preclinical data overwhelmingly indicate that CCK antagonists increase opioid analgesia and decrease antinociceptive tolerance. Perhaps more importantly, however, McCleane has taken this opportunity to explain the lack of clinical trials and the fact that no CCK antagonists are licensed for use with opioids—patent protection for promising drugs, such as proglumide, have expired, thus decreasing enthusiasm and investment from pharmaceutical companies. What is missing from this discussion is a coherent strategy for generating more clinical trials.
As with many textbooks, this one will be somewhat dated by the time of publication. Literature published in 2005–2006 is not reviewed, and only a handful of 2004 articles are discussed. Thus, recent advances published since the author’s previous 2004 review are missing, including an important study by Xie and colleagues describing the contribution of medullary CCK to neuropathic pain (Xie et al., 2005). Other problems include the removal of error bars from the figures, rendering interpretation of the data difficult unless the reader refers to the original articles; numerous typographical and structural errors that also decorated the journal review; discussion of weak or inclusive clinical trials, such as data presented only in abstract form; and inadequate translation of the preclinical data on CCK-A versus CCK-B antagonists toward the interpretation of clinical trials. The author indicates the need for further clinical trials of CCK-A-selective antagonists, but this is confusing because of an earlier assertion suggesting that CCK-B antagonists produce relatively greater potentiation of opioid antinociception in animals.
In summary, for interested readers who do not have free access to the previous journal review (this reviewer had to pay $55 to download the article), this book is essential. This book will also be useful to those readers who have the review, but want a more in-depth discussion of the older literature. On the other hand, this book may fall short for those readers who have the previous review and were hoping for an update of the field. Regardless, it is hoped that this book will encourage governmentsponsored clinical trials for the coadministration of a CCK antagonist with an opioid analgesic, an endeavor that holds considerable promise for the better management of chronic pain.
Reference
Xie, J. Y., Herman, D. S., Stiller, C. O., Gardell, L. R., Ossipov, M. H., Lai, J., et al. (2005). Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance. Journal of Neuroscience, 25(2), 409–416.
Dr. Taylor is associate professor of pharmacology at Tulane University Health Sciences Center, New Orleans, LA.