Role of neurotransmitters, such as PACAP and nociceptin, on the nociceptive transmission in the rat spinal cord.

电生理学研究：采用离体新生大鼠脊髓标本，研究脊髓PAC 1受体在伤害性信息传递中的作用。PAC 1受体激动剂Maxadilan对脊髓腹根的去极化作用呈剂量依赖性。将PAC 1受体拮抗剂Max.d.4应用于脊髓，对背根诱发的慢腹根电位（slow ventral root potential，SVP）产生剂量依赖性的抑制作用。结果表明，新生大鼠脊髓中的PAC 1受体在伤害性信息传递中起重要作用，本实验采用行为学和免疫组织化学方法研究了ORL 1受体在伤害性信息传递中的作用及脊髓中Fos样免疫反应的表达。鞘内注射ORL 1受体激动剂nociceptin可抑制福尔马林诱导的大鼠L5脊髓兴奋行为，并抑制L5脊髓I-II层Fos样免疫反应蛋白的表达。在神经病理性疼痛模型的研究中，预先给予孤啡肽可以延缓坐骨神经慢性压迫性损伤引起的热痛敏的发生，但不能延缓坐骨神经部分损伤引起的热痛敏的发生;预先给予孤啡肽可以抑制坐骨神经慢性压迫性损伤引起的Fos样免疫反应性蛋白的表达，但不能抑制坐骨神经部分损伤引起的Fos样免疫反应性蛋白的表达。这些数据表明，脊髓ORL 1受体的激活抑制大鼠脊髓的伤害性信息传递。

Electrophysiological study:I studied the role of spinal PAC1 receptor on the nociceptive information transmission using an isolated neonatal rat spinal cord preparation. Application of maxadilan to the spinal cord, a PAC1 receptor agonist, resulted in a long lasting ventral root depolarizaion in a dose dependent manner. An application of Max.d.4, a PAC1 receptor antagonist, to the spinal cord produced the depressant effect on the dorsal root evoked slow ventral root potential (slow VRP) in a dose dependent manner. These results suggested that PAC1 receptor in the rat neonatal spinal cord plays an important role in the nociceptive information transmission.Behavioral and Immunohistochemical StudyI examined the role of the opioid receptor like 1 (ORL1) receptor on the nociceptive transmission and thfe expression of Fos-like immunoreactivity of the spinal cord. Intrathecal injection of nociceptin, an ORL1 receptor agonist, depressed the agitation behavior induced by paw formalin injection and inhibited the expression of Fos-like immunoreactivity in the laminae I-II of L5 rat spinal cord. In the study of neuropathic pain model, pre-emptively administered nociceptin delayed the development of thermal hyperalgesia induced by the chronic constriction injury of the sciatic nerve, but not by the partial sciatic nerve injury and depressed the expression of Fos-like immunoreactivity induced by the chronic constriction injury of the sciatic nerve, but not by the partial sciatic nerve injury. These data suggested that activation of spinal ORL1 receptor suppressed the nociceptive transmission in the rat spinal cord.