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.

Inhibition of TRPV1 by SHP-1 in nociceptive primary sensory neurons is critical in PD-L1 analgesia

“…The tumor-induced local environment acidification can activate TRPV1 at normal body temperatures ( 29 , 30 ). TRPV1 has been proved an important ion channel closely related to peripheral sensitization of pain ( 31 – 33 ). Western blot analysis showed significant upregulation of TRPV1 level in DRG tissues ipsilateral to the tumor-bearing bone from PTDs 14 to 28 ( Figure 3A , 1 -way ANOVA, F [4, 14] = 3.83, P = 0.02).…”

Nociceptor plasticity: A closer look

“…This family of channels has been strongly investigated for its pathophysiological and pharmacological interest, for the ubiquitous distribution of the channels in different cell lineages and for the wide range of functions that they absolve. In humans, TRP channels are involved in hot, cold, and taste perception; they are also implied in transducing mechanical stimuli and in some nociceptive perceptions as well (Klein, Trannyguen, Joe, Iodi, & Carstens, ). Several TRP have been discovered in humans: as a matter of fact, 28 different channels have been detected up to date, classified in seven subgroups (TRPC, TRPV, TRPM, TRPP, TRPN, TRPA e TRPML).…”

The Ca2+-Permeable Cation Transient Receptor Potential TRPV3 Channel: An Emerging Pivotal Target for Itch and Skin Diseases

“…Most TRP channels as homo-or probably heterotetramers permeate cations through central nonselective cation entry pores that are symmetrically located in the plasma membrane (Moiseenkova-Bell and Wensel, 2009). In general, TRP channels open and close in response to changes in temperature, chemical stimulation, ligand binding, and weak membrane depolarization (Nilius et al, 2005;Klein et al, 2015;Laing and Dhaka, 2016).…”