Noradrenaline increases hyperalgesia to heat in skin sensitized by capsaicin

Neurophysiological and behavioural observations in animals suggest that sympathetic neural activity and noradrenaline have an excitatory effect on nociceptor discharge in inflamed skin. To determine whether noradrenaline influences pain sensations in humans, heat hyperalgesia in forearm skin sensitized by topical application of 0.6% capsaicin was measured at sites of noradrenaline or saline ionophoresis in 10 healthy subjects. At control sites and sites of saline ionophoresis heat hyperalgesia decreased over the course of the experiment as inflammation subsided. In contrast, heat hyperalgesia persisted at sites of noradrenaline ionophoresis. These findings are consistent with neurophysiological observations that noradrenaline and sympathetic neural stimulation increase nociceptor discharge in inflamed skin, and suggest that sympathetic neural activity might increase pain associated with skin damage.