Yamada Akihiro, Yamada Ayaka I, Ling Jennifer, Gu Jianguo G
Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Mol Pain. 2025 Jan-Dec;21:17448069251359843. doi: 10.1177/17448069251359843. Epub 2025 Jul 5.
Sensing cooling temperatures is achieved by primary afferent endings located in the skin and is essential for the survival of animals. TRPM8 channels, primarily expressed in cutaneous C-fibers, have been established as receptors for cooling temperatures, sensing innocuous cooling from the normal skin temperature near 30°C to 17°C, and noxious cooling below 17°C. A cooling sensation is also felt when skin temperatures are first elevated to higher temperatures, for example, noxious heat, and then cool down to the normal skin temperature near 30°C. It is currently not clear what types of cutaneous afferent fibers are involved in sensing the cooling from a high heat to the normal skin temperature. Cutaneous Aβ-fiber low-threshold mechanoreceptors (Aβ-LTMRs) are primarily involved in the sense of touch and are thought to play no role in cooling sensation. In the present study, we conducted the opto-electrophysiological recordings from the skin-nerve preparations made from the hindpaw glabrous skin of Nav1.8-ChR2 transgenic mice. In these transgenic mice, Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors are primarily Aβ-LTMRs, and Nav1.8-ChR2-positive Aβ-fiber mechanoreceptors are mainly high-threshold mechanoreceptors (Aβ-HTMRs). Neither Aβ-LTMRs nor Aβ-HTMRs responded to temperature rising from 30°C to the noxious heat of 43°C. However, a subpopulation of Aβ-LTMRs, but not Aβ-HTMRs, robustly fires action potential impulses in response to the temperature drop from 43°C to 30°C. This finding reveals for the first time that a subpopulation of Aβ-LTMRs senses the cooling for a temperature drop from noxious heat to normal skin temperature.
感知凉爽温度是通过位于皮肤中的初级传入神经末梢实现的,这对动物的生存至关重要。TRPM8通道主要在皮肤C纤维中表达,已被确立为凉爽温度的感受器,可感知从接近30°C的正常皮肤温度到17°C的无害凉爽,以及低于17°C的有害凉爽。当皮肤温度首先升高到更高温度,例如有害热,然后冷却到接近30°C的正常皮肤温度时,也会感觉到凉爽。目前尚不清楚哪种类型的皮肤传入纤维参与感知从高温到正常皮肤温度的冷却过程。皮肤Aβ纤维低阈值机械感受器(Aβ-LTMRs)主要参与触觉,被认为在凉爽感觉中不起作用。在本研究中,我们对Nav1.8-ChR2转基因小鼠后爪无毛皮肤制成的皮肤-神经标本进行了光电生理记录。在这些转基因小鼠中,Nav1.8-ChR2阴性Aβ纤维机械感受器主要是Aβ-LTMRs,而Nav1.8-ChR2阳性Aβ纤维机械感受器主要是高阈值机械感受器(Aβ-HTMRs)。Aβ-LTMRs和Aβ-HTMRs对温度从30°C升高到43°C的有害热均无反应。然而,Aβ-LTMRs的一个亚群,而不是Aβ-HTMRs,在温度从43°C下降到30°C时强烈发放动作电位冲动。这一发现首次揭示了Aβ-LTMRs的一个亚群可感知从有害热到正常皮肤温度的降温过程。