title: Depletion of noradrenaline inhibits electrically-evoked pain in the skin of the human forearm.
abstract: Guanethidine displaces noradrenaline from sympathetic varicosities, and blocks sympathetic noradrenergic neurotransmission by inhibiting the release of noradrenaline from depleted neural stores. The aim of this study was to determine whether depletion of noradrenaline with guanethidine would oppose thermal hyperalgesia and/or electrically-evoked pain in mildly-burnt skin. Guanethidine was transferred by iontophoresis into a small patch of skin on the forearm of 35 healthy human subjects. The heat-pain threshold to a temperature gradient that increased at 0.5 degrees C/s was then measured at the guanethidine site, a nearby saline-control iontophoresis site, and in untreated skin. In addition, participants rated pain intensity to a 47 degrees C 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 (0.2 mA direct current for 4 min). 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-evoked 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.
authors.affiliation: School of Psychology, Murdoch University, Perth, 6150 Western Australia, Australia. P.Drummond@murdoch.edu.au
authors.forename: Peter D
authors.initials: PD
authors.lastname: Drummond
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D005542:Forearm; D006145:Guanethidine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology*; D007478:Iontophoresis; D008875:Middle Aged; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D012867:Skin / Q000378:metabolism / Q000503:physiopathology*; D013471:Sunburn / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D009638:Norepinephrine; D006145:Guanethidine