Transient receptor potential vanilloid type-1 (TRPV-1) channels contribute to cutaneous thermal hyperaemia in humans

Abstract

The initial, rapid increase in skin blood flow in response to direct application of heat is thought to be mediated by an axon reflex, which is dependent on intact cutaneous sensory nerves. We tested the hypothesis that inhibition of transient receptor potential vanilloid type 1 (TRPV-1) channels, which are putative channels located on sensory nerves, would attenuate the skin blood flow response to local heating in humans. Ten subjects were equipped with four microdialysis fibres which were randomly assigned one of four treatments: (1) vehicle control (90% propylene glycol + 10% lactated Ringer solution); (2) 20 mm capsazepine to inhibit TRPV-1 channels; (3) 10 mm l-NAME to inhibit NO synthase; and (4) combined 20 mm capsazepine + 10 mm l-NAME. Following baseline measurements, the temperature of skin heaters was increased from 33• C to 42• C at a rate of 1.0 • C every 10 s and local temperature was held at 42• C for 20-30 min until a stable plateau in skin blood flow was achieved. An index of skin blood flow was measured directly over each microdialysis site via laser-Doppler flowmetry (LDF). Beat-by-beat blood pressure was measured via photoplethysmography and verified via automated brachial auscultation. At the end of the local heating protocol, temperature of the heaters was increased to 43• C and 28 mm nitroprusside was infused to achieve maximal vasodilatation. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure and normalized to maximal values (%CVC max ). Initial peak in capsazepine (44 ± 4%CVC max ), l-NAME (56 ± 4%CVC max ) and capsazepine + l-NAME (32 ± 6%CVC max ) sites was significantly attenuated compared to control (87 ± 5%CVC max ; P < 0.001 for all conditions). The plateau phase of thermal hyperaemia was significantly attenuated in capsazepine (73 ± 6%CVC max ), l-NAME (47 ± 5%CVC max ) and capsazepine + l-NAME (31 ± 7%CVC max ) sites compared to control (92 ± 5%CVC max ; P < 0.001 for all conditions). These data suggest TRPV-1 channels contribute substantially to the initial peak and modestly to the plateau phases of thermal hyperaemia. These data further suggest a portion of the NO component of thermal hyperaemia may be due to activation of TRPV-1 channels.

Transient receptor potential vanilloid type 1 channels contribute to reflex cutaneous vasodilation in humans

“…Our laboratory has shown previously this vehicle of 90% propylene glycol in 10% lactated Ringer does not result in vasodilation (i.e., there is no baseline shift), and 20 mM capsazepine significantly attenuates the initial peak phase of cutaneous thermal hyperemia in response to local heating (29). We, and others, have previously shown that a 10 mM concentration of L-NAME adequately inhibits NO synthase in human skin (7, 10, 20, 28, 30 -33).…”

“…All drugs were infused for at least 60 min before commencement of whole body heating (10,28,29). To initiate whole body heating, subjects were covered with a plastic water-impermeable rain suit to minimize evaporative heat loss, and 50°C water was circulated through the water-perfused suit.…”

“…Maximal cutaneous vasodilation was elicited via infusion of sodium nitroprusside (SNP) at a rate of 2 l/min and increasing the temperature of the local heating units to 43°C. This temperature increase and dose of SNP have been previously determined effective in eliciting a maximal skin blood flow response (10,12,20,21,28,29).…”

Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus

“…Although the present study did not directly investigate TRP channels, they are considered to be heat sensing and, more importantly, pain sensing. Recently, Wong & Fieger (2010) reported that TRPV1 channels contributed to the cutaneous thermal hyperaemia response in skin. Thus, a painful heat stress localized to a small area of skin, as used in the present study, might induce an autonomic response via TRPV1 stimulation, causing a rapid and exaggerated vasodilator response.…”

“…This notable feature suggested a significant role for thermally sensitive afferents in the forearm dermis. More recently, Wong & Fieger (2010) determined that transient receptor potential vanilloid type 1 (TRPV1) channels localized within sensory afferents contribute greatly to the initial peak and nadir of the hyperaemic response. Much of the work investigating TRP channels has identified a subfamily of vanilloid receptors with pain-and heat-sensing capabilities, yet their individual activation thresholds exhibit clear distinctions Willis, 2009).…”