The flare response to noxious stimulation of the skin is mediated by polymodal nociceptors of C fiber primary afferent nerves. Topical application of capsaicin initiates a flare response and burning pain. In this study, the variability of capsaicin-induced flare and pain was assessed in 220 subjects. The major factors in flare response are body site and age; more severe reactions occur in more proximal sites and in younger subjects. Larger flares were shown to be associated with greater pain. Variability is probably due to differences in the structure and reactivity of the neurovascular unit as proposed in the Lewis model of the axon reflex. It may prove possible to assess polymodal nociceptor function using topical capsaicin in disease states that affect the peripheral terminals of primary afferent nerves.

The function of cutaneous primary afferent unmyelinated nerves (C-fibres) was assessed by measuring axon reflex vasodilatation in the skin over the arms and feet of 15 elderly patients with chronic venous ulcers using a laser Doppler flowmeter. Dilatation of skin microvasculature in response to nerve-independent stimuli was also assessed. Results were compared with those of control subjects matched for age and sex. The chronic venous ulcer group showed reduced axon reflex vasodilatation in the feet but not the arms. Response to nerve-independent vasodilators was similar in both ulcer patients and controls in arms and feet. Local impairment of C-fibre function may partly explain the increased incidence and resistance to healing of leg ulcers in old people.