Reciprocal effects of capsaicin and menthol on thermosensation through regulated activities of TRPV1 and TRPM8.

Masayuki Takaishi,Hiroshi Matsui,Fumitaka Fujita,Yoshiro Suzuki,Makoto Tominaga,Tadashi Shimada,Kunitoshi Uchida

doi:10.1007/s12576-015-0427-y

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is activated by elevated temperature (>42 °C), and it has been reported that cold temperature decreases capsaicin-induced TRPV1 activity. In contrast, transient receptor potential melastatin 8 (TRPM8) is activated by low temperatures and menthol, and heat stimulation suppresses menthol-evoked TRPM8 currents. These findings suggest that the effects of specific agents on TRPV1 and TRPM8 channels are intricately interrelated. We examined the effects of menthol on human (h)TRPV1 and of capsaicin on hTRPM8. hTRPV1 currents activated by heat and capsaicin were inhibited by menthol, whereas hTRPM8 currents activated by cold and menthol were similarly inhibited by capsaicin. An in vivo sensory irritation test showed that menthol conferred an analgesic effect on the sensory irritation evoked by a capsaicin analogue. These results indicate that in our study the agonists of TRPV1 and TRPM8 interacted with both of these channels and suggest that the anti-nociceptive effects of menthol can be partially explained by this phenomenon.Electronic supplementary materialThe online version of this article (doi:10.1007/s12576-015-0427-y) contains supplementary material, which is available to authorized users.

Highlights

Transient receptor potential (TRP) channels respond to a wide variety of sensory stimuli, including temperature, nociceptive compounds, touch, osmolarity, and pheromones [1,2,3]
Menthol inhibited human TRPV1 (hTRPV1) activity induced by capsaicin, and capsaicin inhibited hTRPM8 activity induced by menthol
We first examined the effects of menthol on hTRPV1 and the influence of capsaicin on hTRPM8 in Human embryonic kidney (HEK)-derived 293T (HEK293T) cells expressing hTRPV1 or hTRPM8 using a Ca2?-imaging method at room temperature

Summary

Introduction

Transient receptor potential (TRP) channels respond to a wide variety of sensory stimuli, including temperature, nociceptive compounds, touch, osmolarity, and pheromones [1,2,3]. 10 % of small-diameter sensory neurons in the rat express TRPM8 but not TRPV1 [7, 19], which is consistent with observations of no TRPM8 and TRPV1 colocalization in the majority of studies using TRPM8 antibodies [20,21,22,23]. These results suggest that different nerve fibers are devoted to sensing cold and hot temperatures [24]

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