Faden A I, Molineaux C J, Rosenberger J G, Jacobs T P, Cox B M
Ann Neurol. 1985 Apr;17(4):386-90. doi: 10.1002/ana.410170414.
It has been postulated that endogenous opioids play a pathophysiological role in spinal cord injury, based on the therapeutic effects of the opiate receptor antagonist naloxone in certain experimental models. The high doses of naloxone required to exert a therapeutic action suggest that naloxone's effects may be mediated by non-mu opiate receptors, such as the kappa receptor. This notion is supported by recent pharmacological studies demonstrating that an opiate antagonist more active at kappa sites is effective and far more potent than naloxone in improving outcome after spinal cord injury. Moreover, dynorphin--postulated to be the endogenous ligand for the kappa receptor--is unique among opioids in producing hindlimb paralysis following intrathecal administration in the rat. In the present studies we have examined changes in endogenous opioid immunoreactivity following traumatic spinal cord injury in the rat. Dynorphin A was found to increase progressively with graded injury; changes were restricted to the injury segment and adjacent areas and were time dependent. Dynorphin A-(1-8) showed no marked changes. Methionine and leucine enkephalin were either unaltered or reduced at the injury site; changes were not well localized and were not clearly related to the injury variables. These findings provide further support for a potential pathophysiological role of prodynorphin-derived peptides in spinal cord injury.
基于阿片受体拮抗剂纳洛酮在某些实验模型中的治疗作用，有人推测内源性阿片类物质在脊髓损伤中发挥病理生理作用。发挥治疗作用所需的高剂量纳洛酮表明，纳洛酮的作用可能由非μ阿片受体介导，如κ受体。近期的药理学研究支持了这一观点，这些研究表明，一种在κ位点更具活性的阿片拮抗剂在改善脊髓损伤后的预后方面有效且比纳洛酮更具效力。此外，强啡肽（被认为是κ受体的内源性配体）在阿片类物质中独一无二，经鞘内注射给大鼠后会导致后肢麻痹。在本研究中，我们检测了大鼠创伤性脊髓损伤后内源性阿片免疫反应性的变化。发现强啡肽A随损伤程度的增加而逐渐增加；变化局限于损伤节段及相邻区域，且具有时间依赖性。强啡肽A-（1-8）无明显变化。蛋氨酸脑啡肽和亮氨酸脑啡肽在损伤部位要么未改变，要么减少；变化定位不明确，且与损伤变量无明显关联。这些发现进一步支持了前强啡肽衍生肽在脊髓损伤中潜在的病理生理作用。
