Distinct neurochemical features of acute and persistent pain.
To address the neurochemistry of the mechanisms that underlie the development of acute and persistent pain, our laboratory has been studying mice with deletions of gene products that have been implicated in nociceptive processing. We have recently raised mice with a deletion of the preprotachykinin-A gene, which encodes the peptides substance P (SP) and neurokinin A (NKA). These studies have identified a specific behavioral phenotype in which the animals do not detect a window of "pain" intensities; this window cuts across thermal, mechanical, and chemical modalities. The lowered thermal and mechanical withdrawal thresholds that are produced by tissue or nerve injury, however, were still present in the mutant mice. Thus, the behavioral manifestations of threshold changes in nociceptive processing in the setting of injury do not appear to require SP or NKA. To identify relevant neurochemical factors downstream of the primary afferent, we are also studying the dorsal horn second messenger systems that underlie the development of tissue and nerve injury-induced persistent pain states. We have recently implicated the gamma isoform of protein kinase C (PKCgamma) in the development of nerve injury-induced neuropathic pain. Acute pain processing, by contrast, is intact in the PKCgamma-null mice. Taken together, these studies emphasize that there is a distinct neurochemistry of acute and persistent pain. Persistent pain should be considered a disease state of the nervous system, not merely a prolonged acute pain symptom of some other disease conditions.
Departments of Anatomy and Physiology and W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, CA 94143, USA. aib@phy.ucsf.edu
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D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009448:Neurochemistry / Q000379:methods; D015288:Neurokinin A / Q000235:genetics; D010146:Pain / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism; D011498:Protein Precursors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013373:Substance P / Q000235:genetics; D015320:Tachykinins / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D007527:Isoenzymes; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D015288:Neurokinin A; C087857:protein kinase C gamma; D011493:Protein Kinase C