Nitroprusside inhibits thermal hyperalgesia induced by noradrenaline in capsaicin-treated skin.
A facilitatory effect of the sympathetic neurotransmitter noradrenaline on nociceptor discharge may sometimes contribute to pain and hyperalgesia in inflammatory and neuropathic pain syndromes. Our previous studies have shown that noradrenaline heightens sensitivity to heat in skin sensitized by the topical application of capsaicin, and that this effect persists during arterial occlusion (Drummond, P.D., Noradrenaline increases hyperalgesia to heat in skin sensitized by capsaicin, Pain, 60 (1995) 311-315; Drummond, P.D., Independent effects of ischaemia and noradrenaline on thermal hyperalgesia in capsaicin-treated skin, Pain, 67 (1996) 129-133). In the present study, the hyperalgesic effects of arterial occlusion and the vasodilators nitroprusside and isoprenaline were investigated in the capsaicin-treated skin of healthy subjects, to determine whether adrenergic vasoconstriction contributes to thermal hyperalgesia. Thermal hyperalgesia intensified during arterial occlusion; however, sites of noradrenaline iontophoresis were more sensitive to heat than elsewhere in the capsaicin-treated skin, even when noradrenaline was administered during arterial occlusion. Nitroprusside inhibited adrenergic hyperalgesia except during arterial occlusion, suggesting that the analgesic effect of nitroprusside was mediated by vasodilatation. The beta-adrenoceptor agonist isoprenaline did not antagonize the vasoconstrictive or hyperalgesic effects of noradrenaline, and did not influence thermal hyperalgesia elsewhere in the capsaicin-treated skin. These findings favour an ischaemic mechanism of adrenergic hyperalgesia in skin sensitized by capsaicin. An additional mechanism, independent of skin perfusion, is needed to account for the development of adrenergic hyperalgesia during arterial occlusion.
Drummond
P D
PD
Department of Psychology, Murdoch University, Perth, Western Australia, Australia. drummond@central.murdoch.edu.au
D000293:Adolescent; D000328:Adult; D002211:Capsaicin / Q000008:administration & dosage; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007478:Iontophoresis; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D002211:Capsaicin; D009638:Norepinephrine