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Am J Physiol Regul Integr Comp Physiol 293: R2128-R2135, 2007. First published August 29, 2007; doi:10.1152/ajpregu.00377.2007
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REPORT

SLEEP AND TEMPERATURE REGULATION

Application of menthol to the skin of whole trunk in mice induces autonomic and behavioral heat-gain responses

Koji Tajino,1 Kiyoshi Matsumura,2 Kaori Kosada,1 Tetsuro Shibakusa,3 Kazuo Inoue,3 Tohru Fushiki,3 Hiroshi Hosokawa,1 and Shigeo Kobayashi1

1Deptartment of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Kyoto, Japan; 2Faculty of Information Science and Technology, Osaka Institute of Technology, Hirakata, Osaka, Japan; and 3Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan

Submitted 29 May 2007 ; accepted in final form 25 August 2007

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.

thermoregulation; transient receptor potential channel(s); metabolism



Address for reprint requests and other correspondence: S. Kobayashi, Dept. of Intelligence Science and Technology, Graduate School of Informatics, Kyoto Univ., Kyoto, Japan 606-8501 (e-mail: skoba{at}i.kyoto-u.ac.jp)




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Exp PhysiolHome page
S. F. Morrison, K. Nakamura, and C. J. Madden
Central control of thermogenesis in mammals
Exp Physiol, July 1, 2008; 93(7): 773 - 797.
[Abstract] [Full Text] [PDF]




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