• T Hoffmann, K Kistner, F Miermeister, R Winkelmann, J Wittmann, M J M Fischer, C Weidner, and P W Reeh.
• Institute for Physiology and Pathophysiology, Universitaetsstrasse 17, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany.
• Eur J Pain. 2013 Nov 1;17(10):1472-82.

BackgroundTwo 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.MethodsIn 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.ResultsHeat 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-/-.ConclusionsOur 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.© 2013 European Federation of International Association for the Study of Pain Chapters.

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