Pharmacological activation of skin TRPM8 in mice evokes autonomic and behavioral responses against cooling, resulting in hyperthermia.

Abstract

When ambient temperature is decreased, mammals exert autonomic and behavioral thermoregulatory responses to keep their core temperatures. However, what molecules trigger these responses is still unclear. Recently, transient receptor potential melastatin-8 (TRPM8) was identified as cooling- and menthol-activated cation channel. We hypothesized that TRPM8 activation triggers autonomic and/or behavioral responses against cooling. All experiments were performed at 27ºC (room temperature). For TRPM8 activation, we used menthol instead of cooling. We applied 10% menthol in ethanol to mice skin, and measured core temperatures and autonomic and behavioral responses. Significant elevation of core temperatures (hyperthermia) was observed between 20 min and 2 h 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, tail skin vasoconstriction and heat-seeking behavior, all of which are typical responses against cooling. We conclude that TRPM8 activation triggers autonomic and behavioral thermoregulatory responses against cooling. [J Physiol Sci. 2007;57 Suppl:S88]