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Science 10 October 1997:
Vol. 278. no. 5336, pp. 279 - 283
DOI: 10.1126/science.278.5336.279
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Reports

Preserved Acute Pain and Reduced Neuropathic Pain in Mice Lacking PKCgamma

Annika B. Malmberg, * Chong Chen, Susumu Tonegawa, Allan I. Basbaum

In normal animals, peripheral nerve injury produces a persistent, neuropathic pain state in which pain is exaggerated and can be produced by nonpainful stimuli. Here, mice that lack protein kinase C gamma (PKCgamma ) displayed normal responses to acute pain stimuli, but they almost completely failed to develop a neuropathic pain syndrome after partial sciatic nerve section, and the neurochemical changes that occurred in the spinal cord after nerve injury were blunted. Also, PKCgamma was shown to be restricted to a small subset of dorsal horn neurons, thus identifying a potential biochemical target for the prevention and therapy of persistent pain.

A. B. Malmberg and A. I. Basbaum, Departments of Anatomy and Physiology and W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, CA 92143, USA.
C. Chen and S. Tonegawa, Howard Hughes Medical Institute, Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
*   To whom correspondence should be addressed. E-mail: annikam{at}phy.ucsf.edu

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   Abstract »    Full Text »    PDF »
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