title: Application of menthol to the skin of whole trunk in mice induces autonomic and behavioral heat-gain responses.
abstract: When ambient temperature is decreased in mammals, autonomic and behavioral heat-gain responses occur to maintain their core temperatures. However, what molecules in cutaneous sensory nerve endings mediate cooling-induced responses is unclear. Recently, transient receptor potential melastatin-8 (TRPM8) has been identified in cell bodies of sensory neurons as low-temperature and menthol-activated cation channel. We hypothesized that TRPM8 mediates cooling-induced autonomic and behavioral heat-gain responses. To activate TRPM8 specifically, we applied 1-10% menthol to the skin of whole trunk in mice instead of cooling and measured core temperatures and autonomic and behavioral heat-gain responses. Solvent of menthol (100% ethanol) was used as control. Significant elevation of core temperatures was observed between 20 and 120 min after menthol application. Pretreatment with diclofenac sodium, an antipyretic drug, did not affect this hyperthermia, indicating that the menthol-induced hyperthermia is not fever. Menthol application induced a rise in oxygen consumption, shivering-like muscle activity, tail skin vasoconstriction (autonomic responses), and heat-seeking behavior. All of them are typical heat-gain responses. These results support the hypothesis that TRPM8 mediates cooling-induced autonomic and behavioral heat-gain responses.
authors.affiliation: Dept. of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Kyoto, Japan 606-8501.
authors.forename: Koji
authors.initials: K
authors.lastname: Tajino
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsumura
authors.forename: Kaori
authors.initials: K
authors.lastname: Kosada
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shibakusa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Inoue
authors.forename: Tohru
authors.initials: T
authors.lastname: Fushiki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000982:Antipruritics / Q000008:administration & dosage / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D004576:Electromyography; D007150:Immunohistochemistry; D008297:Male; D008610:Menthol / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D050053:TRPM Cation Channels / Q000235:genetics / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology
chemical_list: D000982:Antipruritics; D016328:NF-kappa B; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D008610:Menthol