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目的观察大鼠下丘脑弓状核(ARC)内微量注射NMDA受体拮抗剂及受体后蛋白激酶抑制剂对神经病理性痛觉过敏的影响,探索脊髓上水平痛觉过敏的中枢敏感化机制。方法建立大鼠坐骨神经部分结扎(PSL)神经病理性疼痛模型,采用压爪缩腿法和辐射热缩腿法测定大鼠的机械痛阈和热痛阈,观测ARC内微量注射MK801(NMDA受体非竞争性拮抗剂)、APV(NMDA受体竞争性拮抗剂)、PP2(Src家族蛋白酪氨酸激酶抑制剂)、GF109203X(蛋白激酶C抑制剂)后70min内PSL模型大鼠痛阈的变化。结果 PSL模型大鼠术后数小时痛阈即明显降低(P<0.05),出现机械痛敏和热痛敏。ARC内微量注射MK801(5nmol)、APV(1.5nmol)后,大鼠机械痛阈和热痛阈明显升高,痛敏现象明显减轻(P<0.05);ARC内注射PP2(5nmol)、GF109203X(0.04nmol)后,痛阈升高幅度更大,痛敏现象也明显减轻(P<0.05)。结论下丘脑弓状核内的NMDA受体及受体后蛋白酪氨酸激酶、蛋白激酶C在痛觉过敏的脊髓上中枢敏感化的形成和维持过程中可能起重要的作用。
Objective To investigate the effects of NMDA receptor antagonists and receptor-derived protein kinase inhibitors on neuropathic hyperalgesia in the hypothalamic arcuate nucleus (ARC) and to explore the central sensitization mechanism of spinal cord hyperalgesia. Methods A rat model of neuropathic pain with partial ligation of sciatic nerve (PSL) was established. The mechanical pain threshold and thermal pain threshold of rats were measured by compression leg reduction method and radiant heat shrinking leg method. Microinjection of MK801 (NMDA receptor non-receptor Competitive antagonist), APV (competitive NMDA receptor antagonist), PP2 (Src family protein tyrosine kinase inhibitor), GF109203X (protein kinase C inhibitor) within 70min after PSL model. Results The pain threshold of PSL model rats was significantly reduced after several hours (P <0.05), mechanical pain and thermal hyperalgesia were observed. The mechanical pain threshold and thermal pain threshold were significantly increased in rats after ARC injection of MK801 (5 nmol) and APV (1.5 nmol), and the pain sensitivity was significantly reduced (P <0.05) 0.04 nmol), the pain threshold increased more significantly and the pain sensitivity was significantly reduced (P <0.05). Conclusion The NMDA receptors and protein tyrosine kinases (PTKs) in hypothalamic arcuate nucleus may play an important role in the formation and maintenance of central sensitization in spinal hyperalgesia.