Thermostat of skin temperature present in nerve endings

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When skin is cooled, cooling-activated receptors in sensory nerves generate impulses as trigger. When these impulses reach and excite their target neurons in the brain, cold sensation occurs at the stimulated skin, inducing heat-seek behavior for thermoregulation. In contrast, when skin is heated, heating-activated receptors generate impulses to induce hot (or warm) sensation at the stimulated skin. Therefore, we have proposed that cooling- and heating activated receptors are thermostats of skin temperature.To analyze properties of thermo receptors, cooling- and heating-activated impulses have been recorded extracellularly since 1950s. However, receptor molecules have not been found for a long time. Recently, several candidate genes for cooling- and heating-activated receptors have been cloned from cell bodies of sensory neurons as thermo TRP channels in TRP (transient receptor potential) non-selective cation channel family.However, it has not been known whether thermo TRP channels are really expressed in nerve endings. TRPM8 is one of the thermo TRP channels, and responds to cooling and menthol. The purpose of this project is to clarify whether TRPM8 is expressed in nerve endings with immuno-histochemical staining of TRPM8 protein. We made anti-TRPM8 antibody with rabbits, and performed immunohistochemical staining of TRPM8 protein in tissue sections of rat tongue. The results showed that TRPM8-positive signal was detected not only in trigeminal ganglion neurons (cell body of sensory neurons) but also in peripheral nerve endings.This is the first report to show that TRPM8, one of the thermo TRP channels, is expressed in peripheral nerve, suggesting that TRPM8 is cooling-activated receptor to induce thermoregulatory behavior. We conclude that TRPM8 is a molecule to act as a thermostat of skin temperature.