title: TRPA1 and TRPV1 are differentially involved in heat nociception of mice.
abstract: BACKGROUND
  Two transient receptor potential (TRP) channels, TRPV1 and TRPA1, have been physiologically studied with regard to noxious heat transduction. Evidence argues against these channels as sole transducers of noxious heat or cold, respectively. Moreover, in submammalian species the TRPA1 orthologue shows heat sensitivity.
  
  
  METHODS
  In vitro, single-fibre and compound action potential recordings from C-fibres as well as measurements of stimulated cutaneous CGRP release are combined with behavioural experiments to assess heat responsiveness in wild type mice, TRPA1 and TRPV1 as well as double-null mutants.
  
  
  RESULTS
  Heat thresholds of cutaneous C-mechano-heat sensitive fibres were significantly higher in TRPA1-/- (43 °C) than +/+ (40 °C) mice, and averaged heat responses were clearly weaker, whereas TRPV1-/- showed normal heat thresholds and responses (up to 46 °C). Compound action potential recordings revealed much less activity-dependent slowing of conduction velocity upon noxious heat stimulation in TRPA1-/- and a delayed deficit in TRPV1-/- in comparison to controls. Heat-induced calcitonin gene-related peptide release was reduced in TRPV1-/- but not TRPA1-/- animals. Paw withdrawal latencies to radiant heat were significantly elevated in TRPA1-/-, more so in TRPV1-/- animals. In general, double-null mutants were similar to TRPV1-/- except for the single-fibre heat responses which appeared as weak as in TRPA1-/-.
  
  
  CONCLUSIONS
  Our results indicate that in addition to TRPV1, TRPA1 plays a role in heat nociception, in particular in definition of the heat threshold, and might therefore serve as a therapeutic target in acute inflammatory pain.
authors.affiliation: Institute for Physiology and Pathophysiology, Universitaetsstrasse 17, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hoffmann
authors.forename: K
authors.initials: K
authors.lastname: Kistner
authors.forename: F
authors.initials: F
authors.lastname: Miermeister
authors.forename: R
authors.initials: R
authors.lastname: Winkelmann
authors.forename: J
authors.initials: J
authors.lastname: Wittmann
authors.forename: M J M
authors.initials: MJ
authors.lastname: Fischer
authors.forename: C
authors.initials: C
authors.lastname: Weidner
authors.forename: P W
authors.initials: PW
authors.lastname: Reeh
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005260:Female; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D059225:Nociception / Q000502:physiology*; D010146:Pain / Q000235:genetics / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D015740:Calcitonin Gene-Related Peptide