Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain

Tissue injuries, with or without involvement of nerves, may lead to ongoing pain and hyperalgesia to external stimuli. In a subset of patients, the pa in is maintained by sympathetic efferent activity (SMP). We investigated if the peripheral administration of the alpha -adrenergic agonist, norepineph rine (NE), in physiologically relevant doses resulted in pain in patients w ith SMP. To establish the dose of intradermal NE required to induce cutaneo us vasoconstriction, NE (1 nM-10 muM, 30 mul) was injected under a laser Do ppler probe on the volar forearm of seven normal subjects. A decrease in bl ood how was evident at a dose of 10 muM Twelve patients (five male, seven f emale) diagnosed to have SMP based on the decrease in pain by a local anest hetic sympathetic blockade (70 +/- 6%) were enrolled in the study. Pain rat ings were obtained continuously for 5 min after intradermal injections of s aline and NE (0.1-10 muM) into their hyperalgesic zone and the mirror-image contralateral side. Injections were done during the period of pain relief following a local anesthetic sympathetic blockade. Similar injections were made in eight control subjects. On the affected side of the patients, the t wo highest concentrations of NE (1 and 10 muM) caused significantly more pa in than saline (P < 0.05, ANOVA). In contrast, there was no significant pai n induced by the NE injections in the unaffected side and in control subjec ts. Six of nine patients tested reported a marked decrease in pain and hype ralgesia following infusion of phentolamine (1 mg/kg over 10 min). Two of t he three patients who did not receive pain relief following phentolamine in fusion also did not report pain to the NE injections. We conclude that NE i njections produce pain in SMP patients at doses that are at the threshold f or producing vasoconstriction. These studies support a role for cutaneous a drenoceptors in the mechanisms of sympathetically maintained pain. (C) 2000 international Association for the Study of Pain. Published by Elsevier Sci ence B.V. All rights reserved.