ALTERED THERMAL HYPERAEMIA IN HUMAN SKIN BY PRIOR DESENSITISATION OF NEUROKININ-1 RECEPTORS

摘要

The neuropeptides substance P (SP) and calcitonin gene-related peptide are believed to be involved in the axon reflex-mediated component of cutaneous thermal hyperaemia, but no studies have specifically addressed this issue. The purpose of this study was to determine whether neurokinin-1 (NK1) receptors, which preferentially bind SP, contribute to the axon-reflex component of cutaneous thermal hyperaemia. Nine subjects were equipped with four microdialysis fibres and received one of four treatments: 1) lactated Ringer’s (control); 2) 10mM L-NAME to inhibit NO synthase; 3) 10μM SP; and 4) 10μM SP + 10mM L-NAME. Skin blood flow was monitored via laser-Doppler flowmetry (LDF) and local skin temperature was controlled using local heating devices. Sites 3 and 4 were perfused with 10μM SP for 15 minutes at a rate of 4μl min⁻¹ and the ensuing vasodilatation was allowed to return to baseline. Following SP-induced vasodilatation, all skin sites were locally heated from a baseline temperature of 33°C to 42°C at a rate of 0.5°C every 5 seconds. Cutaneous vascular conductance (CVC) was calculated as LDF/MAP and normalized to maximal (%CVCmax) via 28mM nitroprusside and local heating to 43°C. Initial peak did not differ between control (79±3%CVCmax) and SP only sites (79±2%CVCmax). Initial peak at L-NAME (43±3%CVCmax) and SP + L-NAME (53±3%CVCmax) sites were significantly reduced compared to both control and SP only sites (p<0.001 for both) and L-NAME sites were attenuated compared to SP + L-NAME sites (p<0.01). There was no observable nadir response at sites pretreated with SP. Compared to control sites (57±4%CVCmax), nadir at L-NAME (14±2%CVCmax) and SP + L-NAME (31±5%CVCmax) sites were significantly reduced (p<0.01 for all conditions). L-NAME significantly reduced the nadir compared to SP + L-NAME (p<0.01). Plateau CVC values did not differ between control (86±3%CVCmax) and SP sites (91±1%CVCmax). At L-NAME (36±4%CVCmax) and SP + L-NAME (56±6%CVCmax) sites, plateau CVC was significantly reduced compared to control and SP only sites (p<0.01 for all conditions). The plateau at L-NAME sites was significantly reduced compared to SP + L-NAME sites (p<0.01). These data suggest NK1 receptors contribute to both the axon reflex component and secondary plateau phase of cutaneous thermal hyperaemia.