Thermosensitive transient receptor potential (TRP) channel agonists and their role in mechanical, thermal and nociceptive sensations as assessed using animal models

Abstract

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, TRPC5) in touch, temperature and pain are reviewed.

Keywords: TRPA1; TRPM8; TRPV1; TRPV3; carvacrol; eugenol; pain; temperature; touch.

Figure 1

Eugenol and carvacrol effects on thermal preference behavior. A: Graph plots the mean percent time that rats occupied each of two adjacent thermoelectric plates, one set at 30 and the other set at 35°C. Rats received topical application to both ventral hindpaws of vehicle, or a low (1%) or high (10%) concentration of eugenol or carvacrol. B: As in A for 30 vs 40°C temperature difference. C. As in A for 30 vs 45°C temperature difference. D. As in A for 30 vs 50°C temperature difference. Error bars: SEM; n=16/group. There were no significant differences between vehicle and eugenol or carvacrol treated animals for any temperature difference (p>0.05, ANOVA).

Figure 2

Concentration-dependent analgesic effects of topically-applied eugenol and carvacrol on thermal hindpaw withdrawal latency (Hargreaves test). A: Eugenol, ipsilateral hindpaw. Eugenol treatment resulted in a concentration-dependent increase in withdrawal latency (analgesia). Thirty percent eugenol was significantly different from 0.1% eugenol (p<0.05, repeated-measures ANOVA). B: Eugenol, contralateral hindpaw. The 30% eugenol treatment was different from all other concentrations (p<0.05, repeated-measures ANOVA). C: Carvacrol, ipsilateral hindpaw. The 30% carvacrol treatment group was significantly different from 10% carvacrol group (p<0.05, repeated-measures ANOVA). Error bars: SEM; n=8/group. D: Carvacrol, contralateral hindpaw, The 30% carvacrol treatment group was significantly different from all other concentrations (p<0.05, repeated-measures ANOVA). Error bars: SEM; n=8/all groups.