INSULIN-DEPENDENT ATTENUATION IN ALPHA(2)-ADRENOCEPTOR-MEDIATED NOCICEPTION IN EXPERIMENTAL DIABETES

Diabetes mellitus is associated with abnormalities in central noradren ergic dynamics, a system that appears to be involved in the regulation of nociception in both humans and experimental animals. To this end, we investigated the responsiveness of nociceptive threshold to the act ions of clonidine (an alpha(2)-adrenoreceptor agonist) and yohimbine ( an alpha(2)-adrenoreceptor antagonist) during diabetes. The induction of diabetes was achieved by the administration of streptozotocin (STZ) (55 mg/kg, intravenously). Nociceptive threshold, as indicated by the tail-flick latency of the tail immersion test, was progressively elev ated as a function of the duration of diabetes. Systemic administratio n of clonidine and yohimbine respectively produced dose-dependent anal gesic and hyperalgesic effects in control animals. Both of these pheno mena were impaired in chronically diabetic animals. In contrast, insul in-treated diabetics displayed supersensitivity to clonidine's antinoc iceptive effect, especially at low doses. Acute hyperglycemia did not interfere with the alpha(2)-agonist-mediated elevation in nociceptive threshold. Attenuation in clonidine antinociceptive effect was also ob served following its intrathecal administration to diabetic animals. O verall, these data suggest that the impaired responsiveness of diabeti c rats might be due to a central alpha(2)-adrenoreceptor desensitizati on and/or biochemicaI defect in the postreceptor events. Copyright (C) 1997 Elsevier Science Inc.