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The aim of this study was to determine whether depletion of noradrenaline with guanethidine would oppose thermal hyperalgesia and\/or electrically\u2010evoked pain in mildly\u2010burnt skin. Guanethidine was transferred by iontophoresis into a small patch of skin on the forearm of 35 healthy human subjects. The heat\u2010pain threshold to a temperature gradient that increased at 0.5\u00b0C\/s was then measured at the guanethidine site, a nearby saline\u2010control iontophoresis site, and in untreated skin. In addition, participants rated pain intensity to a 47\u00b0C stimulus that was applied to each site for 7s. Shortly after the iontophoreses, sensitivity to heat was greater at the guanethidine site than the two control sites, suggesting that ejection of noradrenaline from sympathetic varicosities increased sensitivity to heat. One day later, when neural stores of noradrenaline were depleted, sensitivity to heat did not differ between the guanethidine and control sites. The guanethidine pretreatment did not influence thermal hyperalgesia induced by a mild burn, but inhibited pain evoked by electrical stimulation of the skin (0.2mA direct current for 4min). These findings indicate that ongoing sympathetic neural discharge does not normally influence thermal hyperalgesia in inflamed skin, because depleting noradrenergic stores had no effect. However, electrically\u2010evoked release of noradrenaline may increase nociceptive sensations. Further clarification of this human pain model could provide insights into the mechanism of adrenergic hyperalgesia in certain neuropathic pain syndromes.<\/jats:p>","DOI":"10.1016\/j.ejpain.2007.05.001","type":"journal-article","created":{"date-parts":[[2007,6,22]],"date-time":"2007-06-22T11:22:49Z","timestamp":1182511369000},"page":"196-202","source":"Crossref","is-referenced-by-count":6,"title":["Depletion of noradrenaline inhibits electrically\u2010evoked pain in the skin of the human forearm"],"prefix":"10.1002","volume":"12","author":[{"given":"Peter 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