Thermostat of skin temperature present in nerve endings

当皮肤冷却时，感觉神经中的冷却激活受体产生脉冲作为触发器。当这些脉冲到达并激发大脑中的目标神经元时，受刺激的皮肤就会产生冷感，从而诱导热寻求行为来调节体温。相反，当皮肤被加热时，加热激活的受体产生脉冲，在受刺激的皮肤上诱导热（或温暖）感觉。因此，我们提出了冷却和加热激活受体是皮肤温度的恒温器。为了分析热感受器的特性，自20世纪50年代以来，已经在细胞外记录了冷却和加热激活的脉冲。然而，受体分子很长一段时间没有被发现。近年来，从感觉神经元细胞体中克隆出了多个冷激活受体和热激活受体候选基因，作为TRP（瞬时受体电位）非选择性阳离子通道家族中的热TRP通道。然而，尚不清楚热TRP通道是否真的在神经末梢表达。TRPM8是热TRP通道之一，对冷却和薄荷醇有反应。本项目目的是通过免疫组织化学染色TRPM8蛋白，明确TRPM8是否在神经末梢表达。用家兔制备抗TRPM8抗体，对大鼠舌组织切片进行TRPM8蛋白免疫组化染色。结果表明，trpm8阳性信号不仅存在于三叉神经节神经元（感觉神经元的细胞体）中，也存在于周围神经末梢。这是首次发现TRPM8作为热TRP通道之一在周围神经中表达，提示TRPM8是冷激活受体诱导热调节行为。我们得出结论，TRPM8是一种分子，作为皮肤温度的恒温器。

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.