下丘脑弓状核微量注射NMDA受体拮抗剂和蛋白激酶抑制剂对神经病理性痛觉过敏的抑制作用

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。

Inhibitory Effects of Microinjection of NMDA Receptor Antagonists and Protein Kinase Inhibitors Injected into Arcuate Nucleus on Hyperalgesia Evokedby Neuropathic Pain

Objective To study the mechanism of central sensitization of hyperalgesia at supraspinal level,by observing the effects of microinjection of NMDA receptor antagonists and protein kinase inhibitors injected into arcuate nucleus on the hyperalgesia induced by partial sciatic nerve ligature.Methods The changes of mechanical pain threshold and thermal pain threshold were measured using mechanical withdrawal and thermal withdrawal methods,respectively,after microinjecting MK801（non-competitive NMDA receptor antagonist）,APV（competitive NMDA receptor antagonist）,PP2（Src protein tyrosine kinase inhibitor）,GF109203X（protein kinase C inhibitor） into arcuate nucleus in the period of 70 minutes.Results The pain threshold of rats treated with PSL decreased significantly several hours after operation,mechanical and thermal hyperalgesia appeared at the same time.With microinjecting of MK801（5 nmol） and APV（1.5 nmol） into arcuate nucleus,the pain threshold increased significantly,mechanical and thermal hyperalgesia were inhibited;with microinjecting of PP2（5 nmol） and GF109203X（0.04 nmol）,the pain threshold increased more significantly and hyperalgesia was also inhibited.Conclusion NMDA receptor,Src protein tyrosine kinase and protein kinase C in the hypothalamic arcuate nucleus are involved in the process of central sensitization of neuropathic hyperalgesia.