Thermosensitive Transient Receptor Potential (TRP) Channel Agonists and Their Role in Mechanical, Thermal and Nociceptive Sensations as Assessed Using Animal Models

Introduction: The present paper summarizes research using animal models to investigate the roles of thermosensitive transient receptor potential (TRP) channels in somatosensory functions including touch, temperature, and pain. We present new data assessing the effects of eugenol and carvacrol, agonists of the warmth-sensitive TRPV3, on thermal, mechanical, and pain sensitivity in rats. Methods: Thermal sensitivity was assessed using a thermal preference test, which measured the amount of time the animal occupied one of two adjacent thermoelectric plates set at different temperatures. Pain sensitivity was assessed as an increase in latency of hindpaw withdrawal away from a noxious thermal stimulus directed to the plantar hindpaw (Hargreaves’ test). Mechanical sensitivity was assessed by measuring the force exerted by an electronic von Frey filament pressed against the plantar surface that elicited withdrawal. Results: Topical application of eugenol and carvacrol did not significantly affect thermal preference, although there was a trend toward avoidance of the hotter surface in a 30 vs. 45 °C preference test for rats treated with 1 or 10 % eugenol and carvacrol. Both eugenol and carvacrol induced a concentration-dependent increase in thermal withdrawal latency (analgesia), with no significant effect on mechanosensitivity. Conclusions: The analgesic effect of eugenol and carvacrol is consistent with previous studies. The tendency for these chemicals to increase the avoidance of warmer temperatures suggests a possible role for TRPV3 in warmth detection, also consistent with previous studies. Additional roles of other thermosensitive TRP channels (TRPM8 TRPV1, TRPV2, TRPV4, TRPM3, TRPM8, TRPA1, and TRPC5) in touch, temperature, and pain are reviewed.