title: Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene.
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.
authors.affiliation: Department of Psychology and Centre for Research on Pain, McGill University, Montreal, QC, Canada H3A 1B1.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Mogil
authors.forename: Frank
authors.initials: F
authors.lastname: Miermeister
authors.forename: Frank
authors.initials: F
authors.lastname: Seifert
authors.forename: Kate
authors.initials: K
authors.lastname: Strasburg
authors.forename: Katharina
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Heiko
authors.initials: H
authors.lastname: Reinold
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Austin
authors.forename: Nadia
authors.initials: N
authors.lastname: Bernardini
authors.forename: Elissa J
authors.initials: EJ
authors.lastname: Chesler
authors.forename: Heiko A
authors.initials: HA
authors.lastname: Hofmann
authors.forename: Christian
authors.initials: C
authors.lastname: Hordo
authors.forename: Karl
authors.initials: K
authors.lastname: Messlinger
authors.forename: Kumar V S
authors.initials: KV
authors.lastname: Nemmani
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Rankin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ritchie
authors.forename: Angela
authors.initials: A
authors.lastname: Siegling
authors.forename: Shad B
authors.initials: SB
authors.lastname: Smith
authors.forename: Susana
authors.initials: S
authors.lastname: Sotocinal
authors.forename: Axel
authors.initials: A
authors.lastname: Vater
authors.forename: Sonya G
authors.initials: SG
authors.lastname: Lehto
authors.forename: Sven
authors.initials: S
authors.lastname: Klussmann
authors.forename: Remi
authors.initials: R
authors.lastname: Quirion
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Marshall
authors.initials: M
authors.lastname: Devor
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reeh
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D004594:Electrophysiology; D005260:Female; D005786:Gene Expression Regulation; D006358:Hot Temperature / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009619:Nociceptors / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D013045:Species Specificity
chemical_list: D015740:Calcitonin Gene-Related Peptide