Skin temperature regulation

Skin temperature regulation is a complex physiological process orchestrated primarily by the preoptic area of the hypothalamus to maintain core body temperature homeostasis [1, 7]. This system integrates sensory feedback from peripheral thermoreceptors in the skin, which consist of specialized ion channels in the Transient Receptor Potential (TRP) family, most notably TRPM8 for cold sensing and TRPV1 for heat sensing [5, 7]. These signals drive autonomic and behavioral responses, including cutaneous vasodilation to dissipate heat or vasoconstriction to conserve it, alongside sudomotor activity (sweating) via cholinergic pathways [2, 4]. In pharmacological contexts, the 'target' of skin temperature regulation often refers to the management of vasomotor symptoms like hot flashes, where the Neurokinin 3 receptor (NK3R) on KNDy neurons has emerged as a key regulatory switch [1, 9]. Therapeutic interventions include NK3R antagonists such as fezolinetant, hormone replacement therapies (estrogens), and various agents like clonidine or topical TRP modulators that alleviate thermal discomfort or manage disorders like Raynaud's phenomenon and menopause-related thermoregulatory dysfunction [7, 9, 13]. Dysregulation of this system is central to several clinical conditions, necessitating multi-target approaches across central and peripheral nervous system components [6, 10].

Other names

ThermoregulationVasomotor symptoms (VMS) regulationCutaneous thermoregulationBody temperature control

Neurokinin 3 receptor antagonism, Estrogen receptor agonism, TRPM8 activation or modulation, TRPV1 activation, and Alpha-2 adrenergic agonism.