Role of alpha-2 adrenergic receptors on anesthesia and pain transmission

近十年来，α -2肾上腺素能激动剂如可乐定已被广泛用于临床麻醉，为围手术期患者提供更好的护理。对于接受麻醉和手术的患者，术前给予可口定作为前药，可减少吸入麻醉剂和静脉麻醉剂以及阿片类药物的需求，提供稳定的血流动力学，增强血管加压剂如苯肾上腺素的作用。当鞘内给予可乐定时，可产生强效的脊髓抗痛觉作用，局部麻醉可延长脊髓麻醉时间。为了阐明α -2肾上腺素受体激动剂的作用机制和临床疗效，我们做了一些研究，使用颅窗技术，我们发现可乐定通过激活α -2肾上腺素受体产生脑血管收缩，并呈剂量相关。将α -2肾上腺素能受体激动剂，如克拉定、右美托咪定和替扎尼定注入大鼠的硬膜外腔或静脉注射后，它们的镇痛效果几乎是静脉注射时的5倍。它们的脊髓抗痛觉作用与脊髓和脑α -2肾上腺素能受体结合亲和力的排序相同。吗啡依赖豚鼠脑α -2-肾上腺素受体上调，可乐定可减少吗啡依赖动物的阿片类戒断反应。我们还发现，为减少硬膜外麻醉时肾上腺素试验剂量，在异丙酚麻醉中给予柯定作前药的患者对麻黄碱的反应明显增强。我们还发现，可乐定预用药可改变对α - 1和β - 2肾上腺素能受体激动剂的反应和压力反射敏感性。

For the last decade, alpha-2 adrenergic agonists such as clonidine have been extensively used for clinical anesthesia to provide better patients' care in perioperative periods. When given clonidine preoperatively as a premedicant for patients undergoing anesthesia and surgery it Would reduce requirements of inhalational and intravenous anesthetic agents, and opioids, provide stable hemodynamics, and enhance the action of vasopressors such as phenylephrine. When clonidine given intrathecally, it would produce a potent spinal antinociception and prolonged spinal anesthesia with local anesthetics. To elucidate some of mechanism(s) and roles for clinical efficacy of alpha-2 adrenoceptor agonists, we have done several studies, Using the cranial window technique, we found that clonidine produces cerebral vasoconstriction via activation of alpha-2 adrenoceptors of the pial vessels in a dose-related manner. When alpha-2 adrenoceptor agonists, clonidine, dexmedetomidine and tizanidine, were given into the epidural space or intravenously in rats, they produced almost 5 times greater antinociception with epidural administration as compared with those with their intravenous administration. The rank of order for their spinal antinociceptive action was identical with those of alpha-2 adrenergic receptor binding affinity of spinal' cord and brain. Brain alpha-2-adrenoceptors are up-regulated in morphine dependent guinea pigs and clonidine could reduced opiate withdrawal sings in morphine-dependent animals. We also found that patients given clonidine as premedicant showed a significantly augmented responses to ephedrine in propofol anesthesia to reduce epinephrine test dose for epidural anesthesia. Also we found that clonidine premedication modifies responses to alpha1- and beta-_2 adrenoceptor agonists and baroreflex sensitivity.