Library
APS Bulletin • Volume 18, Number 3, 2008
Resource Reviews
John D. Loeser, MD, Department Editor
Immune and Glial Regulation of Pain
Reviewed by Mitchell B. Max, MD
Joyce A. Deleo, Linda S. Sorkin, and Linda R. Watkins (Eds.). Seattle, IASP Press, 2007. Hard cover with CD-ROM, 443 pages. ISBN 978-0931092-67-1. $95, IASP members $75.
What good is a multiauthor book about emerging scientific findings today when a journal review article can appear online a few months after the author writes it? This is the challenge that editors Joyce DeLeo, Linda Sorkin, and Linda Watkins handily meet Immune and Glial Regulation of Pain. This book deserves a wide readership among basic neuroscientists, translational clinical researchers, and drug developers.
The editors rode worked closely with authors to ensure timely publication with fresh references right up to the 2007 copyright date. The authors used the book’s format to serve multiple audiences. There is extensive detail for the molecular basic scientist who already knows something about glia and lots of clear anatomical and neurochemical diagrams for the clinician or the beginning bench scientist. As a clinical neuropharmacologist trained a few decades ago, I still thought of the brain from a neuron-centered focus, and reading this book subverts this mindset. Leading scientists who study glia in systems apart from pain regale us with the strange features of glia (e.g., networks of astrocytes are internally connected through gap junctions, allowing passage of molecules of up to MW 1000). This makes possible calcium current waves that oscillate through thousands of cells. Microglia and astrocytes respond to and release many of the same immune mediators and transmitters as neurons but have their own favorite molecules, making possible future clinical glial drug interventions by targeting some P2X ATP receptors, IL-10, or glial glutamate transporters.
The book also prompted further reflections (e.g., about how we can optimally expand the field of pain research) (Max, 2003; Max and Stewart, 2008). The National Institutes of Health is beginning to hear our claims that academic pain research is a tiny enterprise compared to pain’s public health impact (Bradshaw et al., 2005; 2008) and to seek advice about expanding pain research. This book is a superb example of how a few researchers can open up domains of innovation for a field. The editors seemed idiosyncratic when they made claims for the importance of spinal cord inflammation in peripheral pains 15 years ago. Now most of the leading pain labs have adopted their program. In retrospect, and upon reading this book, one realizes that the editors were using one of the most time-honored strategies for innovation —“steal from the best”—in adjacent areas of neuroscience. Because so many other areas of medical research are ahead of us, perhaps we can help design funding strategies to more frequently produce this type of innovation. Such a strategy need not be limited to bench science— one could create incentives for young clinical researchers to train in specialties beyond the traditional International Association for the Study of Pain favorites—anesthesiology, neurology, and dentistry (Max and Stewart, 2008; supplementary table).
Another reflection evoked by reading almost any chapter was that DeLeo and colleagues have now made pain neuroscience so much more complicated! One needs to consider the physiology and pharmacology of many types of astrocytes and microglia, not just the exquisitely differentiated neurons. The volume illustrates that occasionally one can get lucky and find a specific molecule whose manipulation will result in pain relief for the whole animal, but one would think that with astrocytes, microglia, and neurons using the same molecules in different ways, only a major computational biology effort will be able make sense of the system. Pain research has lagged behind in computational neurobiology, but the well-studied organization of the peripheral nerve and spinal cord might be a promising model to attract bright neuroscientists from other areas. It seems remarkable that pain scientists have been able to discover interesting new pain mediators by putting several lamina of spinal dorsal horn into a blender (Tegeder et al., 2006; Griffin et al., 2007). The ideas presented in this book argue that we should refine our genomic and proteomic methods to single cells as soon as we can.
I congratulate DeLeo, Sorkin, and Watkins and the IASP Press for finding life in the old format of a bound collection of basic science reviews. If the reader supplements this book new scientific reports, the editors’ thoughtful design will make this volume useful for years to come.
References
Bradshaw, D. H., Nakamura, Y., Chapman, C.R. (2005). National Institutes of Health grant awards for pain, nausea, and dyspnea research: an assessment of funding patterns in 2003. Journal of Pain, 5, 277–293.
Griffin, R. S., Costigan, M., Brenner, G.J., Ma, C.H., Scholz, J., Moss, A., et al. (2007). Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. Journal of Neuroscience, 27,8699–8708.
Max, M. B. (2003). How to move pain and symptom research from the margin to the mainstream. Journal of Pain, 4,355–360.
Max, M. B., Stewart, W. F. The molecular epidemiology of pain: a new discipline for drug discovery. Nat Rev Drug Discovery, 2008, online June 27
Tegeder, I., Costigan, M., Griffin, R.S., Abele, A.A., Belfer, I., Schmidt, H., et al. (2006). GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nature Medicine, 12,1269– 1277.
Dr. Max was Director, Molecular Epidemiology of Pain Program, Center for Pain Research, and Visiting Professor of Anesthesiology and Medicine at the University of Pittsburgh, Pittsburgh, PA.
