Cooling from noxious heat to normal skin temperatures excites a subpopulation of cutaneous Aβ-fiber low-threshold mechanoreceptors

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 degrees C to 17 degrees C, and noxious cooling below 17 degrees 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 degrees 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 A beta-fiber low-threshold mechanoreceptors (A beta-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 A beta-fiber mechanoreceptors are primarily A beta-LTMRs, and Nav1.8-ChR2-positive A beta-fiber mechanoreceptors are mainly high-threshold mechanoreceptors (A beta-HTMRs). Neither A beta-LTMRs nor A beta-HTMRs responded to temperature rising from 30 degrees C to the noxious heat of 43 degrees C. However, a subpopulation of A beta-LTMRs, but not A beta-HTMRs, robustly fires action potential impulses in response to the temperature drop from 43 degrees C to 30 degrees C. This finding reveals for the first time that a subpopulation of A beta-LTMRs senses the cooling for a temperature drop from noxious heat to normal skin temperature.