Bitar M S, Pilcher C W
Department of Pharmacology and Toxicology, School of Medicine, Kuwait University, Safat, Kuwait.
Pharmacol Biochem Behav. 1997 Jan;56(1):15-20. doi: 10.1016/S0091-3057(96)00129-3.
Diabetes mellitus is associated with abnormalities in central noradrenergic 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 actions 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 elevated as a function of the duration of diabetes. Systemic administration of clonidine and yohimbine respectively produced dose-dependent analgesic and hyperalgesic effects in control animals. Both of these phenomena were impaired in chronically diabetic animals. In contrast, insulin-treated diabetics displayed supersensitivity to clonidine's antinociceptive 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 observed following its intrathecal administration to diabetic animals. Overall, these data suggest that the impaired responsiveness of diabetic rats might be due to a central alpha 2-adrenoreceptor desensitization and/or biochemical defect in the postreceptor events.
糖尿病与中枢去甲肾上腺素能动力学异常有关，该系统似乎参与了人类和实验动物的痛觉调节。为此，我们研究了糖尿病期间伤害性感受阈值对可乐定（一种α2-肾上腺素能受体激动剂）和育亨宾（一种α2-肾上腺素能受体拮抗剂）作用的反应性。通过静脉注射链脲佐菌素（STZ）（55mg/kg）诱导糖尿病。如尾浸试验的甩尾潜伏期所示，伤害性感受阈值随着糖尿病病程的延长而逐渐升高。在对照动物中，全身给予可乐定和育亨宾分别产生剂量依赖性的镇痛和痛觉过敏作用。在慢性糖尿病动物中，这两种现象均受损。相比之下，胰岛素治疗的糖尿病患者对可乐定的抗伤害感受作用表现出超敏反应，尤其是在低剂量时。急性高血糖并未干扰α2-激动剂介导的伤害性感受阈值升高。向糖尿病动物鞘内注射可乐定后，其抗伤害感受作用也减弱。总体而言，这些数据表明糖尿病大鼠反应性受损可能是由于中枢α2-肾上腺素能受体脱敏和/或受体后事件中的生化缺陷。
