Effects of partial nerve injury on the responses of C-fiber polymodal nociceptors to adrenergic agonists

The effects of partial division of the great auricular nerve of adult rabbits were evaluated on the responsiveness of cutaneous C-fiber polymodal nociceptors (CPMs) to sympathetic stimulation (SS), close-arterial injections of epinephrine (EPI) and other a-adrenergic agonists. In normal unanesthetized rabbits, the two ears were usually at the same temperature. Two to 4 weeks after partial nerve lesions, however, the operated ear was cooler by 1-3°C in the majority of animals, suggestive of increased vasoconstriction and possible denervation supersensitivity. Neither SS nor EPI (50 ng) excited CPM units (n = 23) from intact anesthetized animals. In contrast, 14-27 days after partial nerve lesions, SS (8 out of 38 units) and EPI (12 out of 38 units) were excitatory for a class of CPMs. There was notable variability in the response of different units and of a given unit between first and second trials. Responses consisted of 1-22 impulses for SS and 1-23 impulses for EPI in the 60 s following a trial. Arterial occlusion did not activate responsive units, suggesting that the excitation was not caused by vascular or temperature changes. Selective a 2-adrenoceptor blockade with yohimbine (0.6 1.0 mg/kg i.v.) or rauwolscine (1.0 mg/kg i.v.) reversibly antagonized the effects of SS and EPI. EPI-responsive units were also excited by norepinephrine (50 ng) and guanabenz (10 μg) but not by clonidine (3 μg) or B-HT 933 (3 μg). The results suggest that circulating EPI, acting via an α-adrenoceptor subtype, can play a part in the development and/or maintenance of aberrant pain syndromes such as causalgia and other sympathetically related dystrophies.