首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Insulin-dependent attenuation in alpha 2-adrenoreceptor-mediated nociception in experimental diabetes.
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Insulin-dependent attenuation in alpha 2-adrenoreceptor-mediated nociception in experimental diabetes.

机译:实验性糖尿病中α2肾上腺素受体介导的伤害感受的胰岛素依赖性衰减。

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摘要

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.
机译:糖尿病与中央去甲肾上腺素能动力学异常有关,该系统似乎参与人类和实验动物的伤害感受调节。为此,我们调查了在糖尿病期间伤害阈值对可乐定(α2肾上腺素受体激动剂)和育亨宾(α2肾上腺素受体拮抗剂)的作用的反应性。糖尿病的诱导是通过链脲佐菌素(STZ)(55 mg / kg,静脉内)给药来实现的。尾巴浸没试验的甩尾潜伏期表明,伤害阈值随糖尿病持续时间的增加而逐渐升高。可乐定和育亨宾的全身性给药分别在对照动物中产生剂量依赖性的镇痛和镇痛作用。这两种现象均在慢性糖尿病动物中受损。相反,胰岛素治疗的糖尿病患者对可乐定的镇痛作用表现出超敏性,尤其是在低剂量时。急性高血糖并不影响α2受体激动剂介导的伤害阈值升高。在鞘内给予糖尿病动物后,还观察到可乐定的抗伤害感受作用减弱。总体而言,这些数据表明糖尿病大鼠的反应能力受损可能是由于受体后事件中的中枢α2-肾上腺素受体脱敏和/或生化缺陷所致。

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