Reversal of nerve ligation-induced allodynia by spinal alpha-2 adrenoceptor agonists.
Reversal of nerve ligation-induced allodynia by spinal alpha-2 adrenoceptor agonists.
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发表时间：
1995
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通讯作者：
T. L. Yaksh;J. W. Pogrel;Youn-Woo Lee;S. Chaplan
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作者：
T. L. Yaksh;J. W. Pogrel;Youn-Woo Lee;S. Chaplan
神经损伤后，可观察到交感神经依赖性异常性疼痛。脊髓α-2激动剂抑制节前神经元。因此检查了α-2激动剂对L5和L 6神经结扎（Chung模型）诱导的异常性疼痛的作用的性质。在大鼠上腰椎（L1-L2）或下颈椎（C5-C6）脊柱节段植入脊髓鞘内导管。神经损伤后，大鼠显示触觉异常性疼痛（平均退缩阈值，羟甲唑啉（14）=胍法辛（17）= 5-溴-6-（2-咪唑啉-2-基氨基）喹喔啉（19）= 2-（2，6-二乙苯基氨基）-2-咪唑啉（21）=可乐定（22）>吗啡（> 30）=甲氧胺（> 30微克）。鞘内注射育亨宾可逆转可乐定和2-（2，6-二乙苯胺基）-2-咪唑啉的作用。在同等剂量下，可乐定通过慢性心室导管或颈髓水平全身给药，产生的抗异常性疼痛作用显著降低。这些结果共同表明，脊髓α-2受体激动剂的抗异常性疼痛作用的网站位于脊髓节前神经元的水平，并对应于他们的能力，以减少节前交感神经流出。吗啡未能发挥抗异常性疼痛作用反映了以下事实：1）阿片类药物在突触前作用于小的初级传入神经，异常性疼痛由大的传入神经输入介导; 2）与α-2激动剂不同，阿片类药物对自主神经流出无影响。
After nerve injury, a sympathetically dependent allodynia may be observed. Spinal alpha-2 agonists inhibit preganglionic neurons. The nature of the effect of alpha-2 agonists on allodynia induced by L5 and L6 nerve ligation (Chung model) was thus examined. Rats were implanted with spinal intrathecal catheters directed at the upper lumbar (L1-L2) or the lower cervical (C5-C6) spinal levels. After nerve injury, rats displayed a tactile allodynia (mean withdrawal thresholds, oxymetazoline (14) = guanfacine (17) = 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (19) = 2-(2,6-diethylphenylamino)-2-imidazoline (21) = clonidine (22) > morphine (> 30) = methoxamine (> 30 micrograms). The effects of clonidine and 2-(2,6-diethylphenylamino)-2-imidazoline were reversed by the intrathecal injection of yohimbine. At equivalent doses, clonidine delivered systemically, i.c.v. by chronic ventricular guides, or at the level of the cervical spinal cord, produced substantially less antiallodynic action. These results jointly suggest that the sites of the antiallodynic action of spinal alpha-2 agonists are located at the level of the spinal preganglionic neurons and correspond to their ability to diminish preganglionic sympathetic outflow. The failure of morphine to exert an antiallodynic action reflects the fact that 1) opiates act presynaptically on small primary afferents and the allodynia is mediated by large afferent input and 2) opiates, unlike alpha-2 agonists do not have an effect on autonomic outflow.