Mu and delta, but not kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rats
Mu and delta, but not kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rats
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DOI：
10.1093/bja/aei285
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发表时间：
2006-01-01
影响因子：
9.8
通讯作者：
Sugahara, K
中科院分区：
文献类型：
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作者：
Kakinohana, M;Nakamura, S;Sugahara, K
背景。在啮齿类动物模型中，主动脉闭塞后短暂间隔后给予鞘内（IT）吗啡，通过脊髓中阿片受体预测的作用诱导短暂性痉挛性截瘫。为了确定脊髓阿片受体亚型的作用，我们研究了各种选择性阿片受体激动剂的 IT 给药是否可以在大鼠短期脊髓缺血后诱导截瘫。方法。在植入 IT 导管的 Sprague-Dawley 大鼠中，使用主动脉内球囊诱导脊髓缺血 6 分钟。再灌注后30分钟，鞘内注射Mu（[d-Ala（2），N-Me Phe（4），Gly-ol（5）]脑啡肽），κ（U50488H）或δ（[d-Pen（2,5）]脑啡肽）选择性激动剂。使用另一组动物来研究对这种运动功能障碍的剂量反应效应。为此，在缺血后鞘内注射三剂 mu、kappa 或 delta 激动剂。 IT注射后，使用运动缺陷指数定期评估运动功能的恢复（0=完全恢复；6=完全截瘫）。结果。 IT 施用 mu 和 delta 而不是 kappa 激动剂在诱导痉挛性截瘫方面产生剂量依赖性效应。此外，IT mu 和 delta 激动剂引起的痉挛可分别被 IT 纳洛酮和纳曲吲哚完全逆转。结论。这些结果表明，短期脊髓缺血后各种阿片类药物对运动功能的影响取决于个体阿片类受体亚型。
Background. Intrathecal (IT) morphine given after a short interval of aortic occlusion in a rodent model induced transient spastic paraparesis via opioid receptor-predicted actions in spinal cord. To determine the role(s) of spinal opioid receptor subtypes we investigated whether IT administration of various selective opioid receptor agonists can induce paraparesis following a short period of spinal cord ischaemia in rats.Methods. In Sprague-Dawley rats implanted with an IT catheter, spinal cord ischaemia was induced for 6 min using an intraaortic balloon. Mu ([d-Ala(2), N-Me Phe(4), Gly-ol(5)] enkephalin), kappa (U50488H) or delta ([d-Pen(2,5)] enkephalin) selective agonists were injected intrathecally 30 min after reperfusion. A separate group of animals was used to investigate the dose-response effect on this motor dysfunction. For this purpose, three doses of mu, kappa, or delta agonists were injected intrathecally after ischaemia. After IT injection, recovery of motor function was assessed periodically using the motor deficit index (0=complete recovery; 6=complete paraplegia).Results. IT administration of mu and delta but not kappa agonists produced dose-dependent effects in the induction of spastic paraparesis. In addition, this spasticity induced by IT mu and delta agonists was reversed completely by IT naloxone and naltrindole, respectively.Conclusion. These results suggest that the effect of various opioids on motor function after a short period of spinal cord ischaemia depends upon individual opioid receptor subtypes.