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NMDA已被证明在慢痛的诱导和维持中起关键作用。NMDA受体的激活可造成Ca2 +的内流 ,从而诱导NO合酶的活化和NO的生成。有资料显示 ,NMDA受体和NO合酶均参与慢痛状态下的脊髓背角神经元的敏感化 ,并认为NMDA受体的很多作用是由NO介导。但是 ,NO作为一种内源性特殊信号分子 ,它在伤害感受中的作用仍在探讨之中 ,例如 ,NO在中枢神经系统是否也参与介导已被熟知的NMDA受体 NO途径之外的其他伤害感受机制 ,目前尚缺少直接的证据。fos蛋白的表达已被广泛接受为脊髓水平伤害感受传递的指标。本研究中使用这一技术 ,结合鞘内应用NMDA受体的非竞争性阻断剂MK 80 1和NO合酶抑制剂L NAME ,探讨了在通用的大鼠坐骨神经切断模型中NMDA受体和NO在背角伤害性感受中的作用 ,并对NO也参与其他神经递质或神经肽活化的伤害感受通路的可能性进行了分析。同时 ,我们选择在神经切断后 2h处死动物 ,以明确神经损伤急性诱导的放电的作用。试验动物预先行鞘内PE 10导管埋植手术。实验当日 ,实验组的动物又分四组 ,分别接受鞘内注射无菌生理盐水 ,MK 80 1,L NAME ,或两药联合注射。用药半小时后切断一侧坐骨神经 ,并于神经切断后 2h处死动物 ,用免疫组化技术 (ABC法 )检测腰部 (L4 5 )脊髓背角中的fos样免疫阳性 (FLI)神经元的数?
NMDA has been shown to play a key role in the induction and maintenance of chronic pain. Activation of NMDA receptors can cause influx of Ca2 + to induce NO synthase activation and NO production. It is reported that both NMDA receptors and NO synthase are involved in sensitization of neurons in the dorsal horn of spinal cord under chronic pain state and that many of the effects of NMDA receptors are mediated by NO. However, the role of NO as an endogenous specific signaling molecule in nociception is still being explored, for example, whether NO is involved in mediating the well-known NMDA receptor NO pathway in the central nervous system Other mechanisms of nociception are currently lacking in direct evidence. The expression of fos protein has been widely accepted as an indicator of nociceptive transmission of spinal cord levels. In this study, we used this technique in combination with intrathecal NMDA receptor non-competitive blocker MK 80 1 and NO synthase inhibitor L NAME, to explore the role of NMDA receptor and NO in general rat sciatic nerve transection model The role of nociception in nociception of the dorsal horn and the possibility that NO is also involved in the nociceptive pathway of other neurotransmitters or neuropeptide activation. At the same time, we chose to sacrifice the animals 2h after nerve transection in order to clarify the effect of an acutely induced discharge of nerve injury. Experimental animals premedicated with intrathecal PE 10 catheter implantation surgery. On the experimental day, animals in the experimental group were divided into four groups, receiving intrathecal sterile saline, MK 80 1, L NAME, or a combination of the two drugs. Half an hour after treatment, the sciatic nerve was cut off and the animals were sacrificed 2 h after the nerve was cut off. The numbers of fos-like immunopositive (FLI) neurons in the spinal dorsal horn of the lumbar (L4 5) were detected by immunohistochemistry (ABC method)