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1Single applications of solutions of capsaicin were made to the intact skin of anaesthetized rats and the effects on cutaneous blood flow and the firing of C-nociceptor afferents determined. Blood flow was measured by laser-Doppler flowmetry. C-fibre activity was recorded from filaments dissected from the saphenous nerve. 2 Following the application of a capsaicin solution (concentration > 1 mM) to rat saphenous skin, low frequency firing occurred in C-polymodal nociceptors that sometimes continued for > 10 min. At the some time, large increases in skin blood flow occurred exceeding 300% in some instances. 3 After the initial excitation, some C-polymodal nociceptors lost their sensitivity to pressure whilst their sensitivity to heat was lost or enhanced depending on the vehicle used. 4 Sensitivity of C-polymodal nociceptors to heat recovered in <1 day following a single application of 33 mM capsaicin. Thresholds to mechanical pressure, however, were still significantly elevated by 123% on day 1, but had recovered on day 2. 5 Vasodilatation in response to saphenous nerve stimulation ('antidromic vasodilatation') was significantly reduced by 35%, 2 days after a single application of 33 mM capsaicin, but was normal at 4 days. 6 Following a single application of 33 mM capsaicin, skin substance P levels fell to only half the normal value at day I and remained at this level throughout the 4 day period examined. 7 It is suggested that the ability of relatively low concentrations of capsaicin to desensitize C-fibre nociceptors may underlie the analgesic action of topical capsaicin in man.

Skin blood flow was monitored during antidromic stimulation of identified cutaneous C fibres in fine filaments dissected from the saphenous nerve of anaesthetized rabbits and rats. The techniques used to monitor skin blood flow were laser Doppler perfusion imaging and laser Doppler flowmetry. In the rabbit filaments a total of thirty‐three C fibres were tested for their ability to produce antidromic vasodilatation. The only C fibres found to have vasodilator actions were of the polymodal nociceptor afferent class, and fourteen (50%) of the twenty‐eight polymodal nociceptor units tested were vasoactive. The afferent receptive fields of polymodal nociceptor afferents were mapped carefully using suprathreshold mechanical stimuli, and there was a good correlation between afferent receptive field area and area of vasodilatation. In the rat, eleven of the fifty‐four C fibres antidromically stimulated had vasodilator actions. All eleven vasoactive C fibres were nociceptive and comprised seven polymodal nociceptor units, two heat nociceptor units and two incompletely classified nociceptor units. The area of increased blood flow was always coincident with the afferent field of the stimulated unit. In the rat the vasodilator units were not evenly distributed over the saphenous nerve receptive field. Nine of the eleven vasoactive C fibres had receptive fields located on the foot or the digits, and only two were on the ankle or lower leg. Overall, the population of nociceptive C fibres was evenly distributed over the saphenous nerve receptive field. In both the rabbit and the rat, a subclass of polymodal nociceptor afferents form the majority of the vasoactive units and will make the main contribution to axon reflex flare and other neurogenic inflammatory responses involving vasodilatation. The vasoactive polymodal nociceptor units tend to have relatively low mechanical sensitivity, although they have typical heat thresholds. In the rat heat nociceptor units also have vasodilator actions. However, such heat nociceptor units form a minor functional class of afferent C fibre in the rat saphenous nerve, and are not found in the rabbit saphenous nerve. The findings from this study in the rabbit and the rat are compared with the situation in pig skin. The close relationship between afferent receptive field area and spread of flare across species is noted, and the way these measures increase with body size is discussed.

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