Disruption of TRPV3 Impairs Heat-Evoked Vasodilation and Thermoregulation: A Critical Role of CGRP

Abstract

Sensing environmental temperature is a key factor allowing individuals to maintain thermal homeostasis via thermoregulatory mechanisms, including changes to skin blood flow. Among transient receptor potential channels, transient receptor potential vanilloid 3 (TRPV3) is a heat-activated cation channel highly expressed in keratinocytes. However, the role of TRPV3 in triggering heat-evoked cutaneous vasodilation is unknown. Using a murine in vivo model of local acute environmental heat exposure in the skin, we show that TRPV3 is involved in the local thermoregulatory control of skin blood flow by initiating the release of calcitonin gene-related peptide and nitric oxide in response to local heating of the skin. In addition to their contribution in local heat-evoked vasodilation, TRPV3, calcitonin gene-related peptide, and nitric oxide also contribute to internal body temperature stability during passive whole-body heating. This study provides in vivo demonstration of the role of TRPV3 as a strong modulator of cutaneous vascular thermoregulatory mechanisms.

Camphor, Applied Epidermally to the Back, Causes Snout- and Chest-Grooming in Rats: A Response Mediated by Cutaneous TRP Channels

“…In heterologous systems in vitro, TRPV3 opens at temperatures >33 °C [14,15], i.e., within the upper range of physiological values of T sk , as observed during skin vasodilation in rats [34]. Furthermore, TRPV3 has been reported to mediate the cutaneous vasodilatation induced by local heating and to play a role in defending the deep T b during heat exposure [35]. Other studies suggest that TRPV3 is involved in the avoidance of innocuous ambient heat in transgenic mice, as well as in thermal pain responses [19,36].…”

“…Other studies suggest that TRPV3 is involved in the avoidance of innocuous ambient heat in transgenic mice, as well as in thermal pain responses [19,36]. Yet, TRPV3 knockout mice show no obvious thermoregulatory phenotype [37] and, specifically, no alterations in the deep T b [19,35]. Overall, there is no consensus as to whether TRPV3 is important in driving thermoregulatory responses, and which responses in particular [16].…”

In Vitro Sensitive Skin Models: Review of the Standard Methods and Introduction to a New Disruptive Technology

“…However, besides this aspect, keratinocytes have been shown to be directly involved in cutaneous sensoriality. Indeed, they can both modulate and initiate sensory perception and sensory neuron response [21,42,43]. Thus, an appropriate model to study skin sensitivity and assess active molecule efficacy on sensitive skin needs to at least contain sensory neurons and keratinocytes (Table 1).…”

“…Nevertheless, some studies revealed that keratinocytes also express diverse sensory receptors, such as TRPV1, TRPV3, and TRPV4 [8,11,20]. Mainly expressed in keratinocytes, TRPV3 can stimulate CGRP secretion, which induces local vasodilation that plays a role in body thermoregulation [21]. The selective activation of the keratinocyte-located TRPV1 and TRPV4 sensors is sufficient to induce pain and itch, respectively [11].…”

Activity analysis of thermal imaging videos using a difference imaging approach

“…Infrared thermal imaging is generally used to capture surface temperature estimates of objects for inference of heat transfer (Tattersall 2016). It has the practical advantage of being non-invasive and yet still provides quantitative thermal information, from which inferences of surface blood flow (Di Carlo 1995;Fromy et al 2018), evaporative cooling (Cadena et al 2013), and localized heat production (Robertson et al 2019) have been recorded. Thermal imaging cameras are capable of both still image and video capture, although typically video capture requires computer-assisted image capture.…”