Effects of Pharmacological Activation of TRPM8 Ion Channels on the Thermoregulatory Responses during Warming

Preliminary non-thermal activation of cold-sensitive TRPM8 ion channel facilitates initiation of the heat-defense responses in homoiothermal animals by decreasing temperature threshold of the vasodilatory response. TRPM8 activation leads to earlier heat-initiated increase in oxygen consumption, but reduces its magnitude. Warming inhibits the lipolytic effect of menthol activation of TRPM8 observed under thermoneutral conditions. Thus, modulation of the skin temperature afferent signal by ion channel agonist TRPM8 changes not only cold-defense, but also heat-defense responses of the body.