LAUSR

Our ability to perceive the external environment and respond appropriately to it is dependent, in part, on functional cutaneous sensory nerves. Sensory nerves and receptors in the skin respond to a host of stimuli, including, but not limited to, temperature. Highlighting the importance of sensory nerve responses to heat, one of the corecipients of the 2021 Nobel Prize in Physiology or Medicine was Dr David Julius, whose pioneering work was largely responsible for unravelling the function of the heat-sensitive transient receptor potential vanilloid type-1 (TRPV1) channel. The skin blood flow response to non-painful local heating is a biphasic response, in which the first (initial peak) phase is mediated largely by sensory nerves and TRPV1 channels, with a modest contribution from nitric oxide (NO), and the second (plateau) phase is mediated predominantly by endothelial NO (Bruning et al., 2012; Kellogg et al., 2008; Minson et al., 2001; Wong & Fieger, 2010). Using the non-painful local heating techniques, one can simultaneously investigate sensory nerve-mediated vasodilatation and endotheliumdependent vasodilatation. Importantly, the sensory nerve-mediated vasodilatation represents an objective, physiological outcome with minimal subjective bias inherent in techniques such as heat-pain thresholds or ratings of heat perception. Clinically, the effect of type 2 diabetes on sensory nerve function and the resultant sensory neuropathy is well known; however, additional data suggest a link between sensory nerve dysfunction and vascular dysfunction in conditions such as hypertension (Cameron et al., 2001). Many studies that assess the skin blood flow response to local heating either do not report the data for the sensory nerve component or mention it in passing, with little focus on the underlying physiological mechanisms. This has led,