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Publication : Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene.

First Author  Mogil JS Year  2005
Journal  Proc Natl Acad Sci U S A Volume  102
Issue  36 Pages  12938-43
PubMed ID  16118273 Mgi Jnum  J:101430
Mgi Id  MGI:3603999 Doi  10.1073/pnas.0503264102
Citation  Mogil JS, et al. (2005) Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene. Proc Natl Acad Sci U S A 102(36):12938-43
abstractText  Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect differential responsiveness of primary afferent thermal nociceptors to heat stimuli. We further present convergent behavioral and electrophysiological evidence that the variable responses to noxious heat are due to strain-dependence of CGRP expression and sensitivity. Strain differences in behavioral response to noxious heat could be abolished by peripheral injection of CGRP, blockade of cutaneous and spinal CGRP receptors, or long-term inactivation of CGRP with a CGRP-binding Spiegelmer. Linkage mapping supports the contention that the genetic variant determining variable heat pain sensitivity across mouse strains affects the expression of the Calca gene that codes for CGRPalpha.
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