Effect of sensory blockade and rate of sensory stimulation on local heating induced axon reflex response in facial skin

Local neuronal circuits in non-glabrous skin drive the initial increase of the biphasic cutaneous vasodilation response to fast non-noxious heating. Voltage-sensitive Na⁺ (NaV) channel inhibition blocks the afferent limb of the non-glabrous forearm cutaneous axon reflex. Slow local heating does not engage this response. These mechanisms have not been adequately investigated or extended into areas associated with flushing pathology. We hypothesized that despite regional differences in sensory afferents, both sensory blockade and slowing the heating rate would abate the cutaneous axon reflex-mediated vasodilator responses in facial skin. We measured skin blood flow responses (laser-Doppler flowmetry) of 6 healthy subjects (5 female) to non-noxious forearm, cheek, and forehead local heating, expressed as a percentage of cutaneous vascular conductance at plateau (CVC = flux/mean arterial pressure). We assessed CVC during fast (1 °C/30s) and slow (1 °C/10 min) local heating to 43 °C in both NaV inhibition (topical 2.5% lidocaine/prilocaine) and control conditions. NaV inhibition decreased forearm (control: 84 ± 4, block: 34 ± 9%plateau, p < 0.001) and trended toward decreased forehead (control: 90 ± 3, block: 68 ± 3%plateau, p = 0.057) initial CVC peaks but did not alter cheek responses (control: 90 ± 3, block: 92 ± 13%plateau, p = 0.862) to fast heating. Slow heating eliminated the initial CVC peak incidence for all locations, and we observed similar results with combined slow heating and NaV inhibition. Slower sensory afferent activation rate eliminated the axon reflex response in facial and non-glabrous skin, but topical sensory blockade did not block axon reflex responses in flushing-prone cheek skin. Thus, slower heating protocols are needed to abate facial, particularly cheek, axon reflex responses.