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脊髓损伤大鼠慢性痛觉过敏的治疗:鞘内注射选择性阿片受体激动剂的效果

Treatment of chronic allodynia in spinally injured rats: effects of intrathecal selective opioid receptor agonists.

作者信息

Hao J X, Yu W, Wiesenfeld-Hallin Z, Xu X J

机构信息

Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.

出版信息

Pain. 1998 Apr;75(2-3):209-17. doi: 10.1016/s0304-3959(97)00221-2.

Abstract

We examined the effects of intrathecal (i.t.) selective opioid receptor agonists in alleviating mechanical and cold allodynia in spinally injured rats. Both DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a mu-opioid receptor agonist) and DPDPE ([D-Phe2,D-Phe5]-enkephalin, a delta-opioid receptor agonist) dose-dependently relieved the chronic allodynia-like behavior at doses selective for their respective receptors. The anti-allodynic effect of DAMGO and DPDPE was reversed by the selective mu- and delta-opioid receptor antagonists CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) and naltrindole, respectively. In contrast, the selective kappa-opioid receptor agonist U50488H did not alleviate the allodynia-like behavior, but rather enhanced it. The anti-nociceptive and anti-allodynic effect of i.t. DAMGO was blocked by U50488H. Thus, activation of spinal mu- and delta-, but not kappa-opioid receptors produced anti-allodynic effect in this model of central pain. Drugs which act selectively on opioid receptor subtypes may be useful in managing chronic central pain of spinal cord origin.

摘要

我们研究了鞘内注射(i.t.)选择性阿片受体激动剂对减轻脊髓损伤大鼠机械性和冷觉异常性疼痛的作用。DAMGO([D-丙氨酸2,N-甲基苯丙氨酸4,甘氨酸5-醇]-脑啡肽,一种μ阿片受体激动剂)和DPDPE([D-苯丙氨酸2,D-苯丙氨酸5]-脑啡肽,一种δ阿片受体激动剂)在各自受体选择性剂量下均呈剂量依赖性地缓解慢性异常性疼痛样行为。DAMGO和DPDPE的抗异常性疼痛作用分别被选择性μ和δ阿片受体拮抗剂CTOP(D-苯丙氨酸-半胱氨酸-酪氨酸-D-色氨酸-鸟氨酸-苏氨酸-青霉胺-苏氨酸-NH2)和纳曲吲哚逆转。相比之下,选择性κ阿片受体激动剂U50488H并未减轻异常性疼痛样行为,反而增强了该行为。鞘内注射DAMGO的抗伤害性和抗异常性疼痛作用被U50488H阻断。因此,在这种中枢性疼痛模型中,脊髓μ和δ阿片受体的激活产生了抗异常性疼痛作用,而κ阿片受体的激活则没有。选择性作用于阿片受体亚型的药物可能有助于治疗脊髓源性慢性中枢性疼痛。

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