Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene.
Document Type
Article
Publication Date
2005
Keywords
Calcitonin-Gene-Related-Peptide, Electrophysiology, Gene-Expression-Regulation, Hot-Temperature, Mice-Inbred-Strains, Nociceptors, Pain-Measurement, Pain-Threshold, Species-Specificity
First Page
12938
Last Page
12943
JAX Source
Proc Natl Acad Sci U S A 2005 Sep; 102(36):12938-43.
Abstract
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.
Recommended Citation
Mogil JS,
Miermeister F,
Seifert F,
Strasburg K,
Zimmermann K,
Reinold H,
Austin JS,
Bernardini N,
Chesler EJ,
Hofmann HA,
et a.
Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene. Proc Natl Acad Sci U S A 2005 Sep; 102(36):12938-43.