Long J B, Rigamonti D D, de Costa B, Rice K C, Martinez-Arizala A
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Brain Res. 1989 Sep 11;497(1):155-62. doi: 10.1016/0006-8993(89)90982-7.
The selective kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) was used to distinguish a kappa opioid component in the mechanisms underlying the hindlimb paralysis, ischemia, and neuronal injury induced in the rat by the kappa opioid agonist dynorphin A. Spinal intrathecal (i.t.) injection of nor-BNI (20 nmol) either 15 min or immediately before i.t. injections of 5 or 20 nmol of dynorphin A failed to alter the dynorphin A-induced disruption of hindlimb motor function and nociceptive responsiveness. Nor-BNI also did not change the 3-fold increases in cerebrospinal fluid lactate concentrations produced by 20 nmol of dynorphin A. Neuroanatomical evaluations revealed that the cell loss, fiber degeneration, and central gray necrosis in lumbosacral spinal cords of rats treated with 20 nmol of dynorphin A were not altered by nor-BNI (20 nmol, i.t.). Thus, the spinal cord injury and associated neurological deficits resulting from i.t. injection of dynorphin A appear to be primarily, if not totally, attributable to its non-kappa opioid action(s).
选择性κ阿片受体拮抗剂去甲二氢吗啡酮（nor-BNI）被用于区分κ阿片类药物成分在κ阿片激动剂强啡肽A诱导的大鼠后肢麻痹、缺血和神经元损伤机制中的作用。在鞘内注射5或20 nmol强啡肽A前15分钟或立即鞘内注射20 nmol去甲二氢吗啡酮，均未能改变强啡肽A诱导的后肢运动功能破坏和伤害性反应。去甲二氢吗啡酮也未改变20 nmol强啡肽A引起的脑脊液乳酸浓度3倍的升高。神经解剖学评估显示，鞘内注射20 nmol去甲二氢吗啡酮对鞘内注射20 nmol强啡肽A处理的大鼠腰骶脊髓中的细胞丢失、纤维变性和中央灰质坏死无影响。因此，鞘内注射强啡肽A导致的脊髓损伤及相关神经功能缺损，即便不是完全由其非κ阿片类作用引起，也主要归因于此。
