title: Reciprocal effects of capsaicin and menthol on thermosensation through regulated activities of TRPV1 and TRPM8.
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.
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan. takaishi-m@mandom.co.jp.|Mandom Corporation, Osaka, 540-8530, Japan. takaishi-m@mandom.co.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takaishi
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan. kuchida@nips.ac.jp.|Department of Physiological Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, 444-8585, Japan. kuchida@nips.ac.jp.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan. yoshiro@nips.ac.jp.|Department of Physiological Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, 444-8585, Japan. yoshiro@nips.ac.jp.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Mandom Corporation, Osaka, 540-8530, Japan. matsui-h@mandom.co.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Mandom Corporation, Osaka, 540-8530, Japan. shimada-ta@mandom.co.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan. fujita-f@mandom.co.jp.|Mandom Corporation, Osaka, 540-8530, Japan. fujita-f@mandom.co.jp.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Fujita
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan. tominaga@nips.ac.jp.|Department of Physiological Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, 444-8585, Japan. tominaga@nips.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000328:Adult; D000700:Analgesics / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D002460:Cell Line; D003080:Cold Temperature; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D010147:Pain Measurement / Q000379:methods; D050053:TRPM Cation Channels / Q000819:agonists / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000700:Analgesics; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D008610:Menthol; D002211:Capsaicin
keywords: Analgesic; Capsaicin; Menthol; TRPM8; TRPV1