Hao J X, Yu W, Xu X J, Wiesenfeld-Hallin Z
Department of Laboratory Medical Sciences and Technology, Huddinge University Hospital, Karolinska Institute, Sweden.
Brain Res. 1996 Oct 14;736(1-2):28-34. doi: 10.1016/0006-8993(96)00703-2.
A chronic pain-like response to innocuous mechanical stimuli (allodynia) was observed in rats after severe spinal cord ischemia, which resembled some painful conditions observed in spinally injured patients. The present studies examined the effects of clonidine, an alpha 2-adrenoceptor agonist, on this allodynia-like response. Intrathecal (i.t.) clonidine dose-dependently relieved allodynia and doses up to 10 micrograms did not induce motor deficits or sedation, but slightly increased systemic blood pressure. The anti-allodynic effect of i.t. clonidine was reversed by the selective alpha 2-adrenoceptor antagonist atipamezole. In contrast, 50 and 100 micrograms/kg intraperitoneal (i.p.) clonidine did not relieve the chronic allodynia, although the higher dose induced some motor deficits and sedation. Allodynic behavior was abolished after 200 micrograms/kg, i.p. clonidine, which, however, caused strong sedative and motor impairment. The present data suggested that spinal, but not systemic, alpha 2-adrenoceptor agonists may have therapeutic value in treating mechanical allodynia in patients with neuropathic pain of spinal origin.
在严重脊髓缺血后的大鼠中观察到对无害机械刺激的慢性疼痛样反应（异常性疼痛），这类似于在脊髓损伤患者中观察到的一些疼痛状况。本研究考察了α2肾上腺素能受体激动剂可乐定对这种异常性疼痛样反应的影响。鞘内注射可乐定剂量依赖性地减轻异常性疼痛，高达10微克的剂量不会引起运动功能缺损或镇静作用，但会使全身血压略有升高。鞘内注射可乐定的抗异常性疼痛作用可被选择性α2肾上腺素能受体拮抗剂阿替美唑逆转。相比之下，腹腔注射50和100微克/千克的可乐定不能减轻慢性异常性疼痛，尽管较高剂量会引起一些运动功能缺损和镇静作用。腹腔注射200微克/千克的可乐定后异常性疼痛行为消失，然而，这会导致强烈的镇静和运动功能损害。目前的数据表明，脊髓而非全身的α2肾上腺素能受体激动剂可能对治疗脊髓源性神经病理性疼痛患者的机械性异常性疼痛具有治疗价值。
