术后鞘内给予经典型AMPA/KA受体拮抗剂有很强的镇痛效应，但副作用妨碍了临床使用。由于经典型AMPA/KA受体拮抗剂对KA受体的选择性相对较高，提示KA受体在术后痛敏中有更重要作用。最新研究发现，KA受体具有独特的功能调节机制，然而这些功能调节过程是否参与痛觉敏化尚不清楚。基于预实验结果，我们推测术后脊髓背角KA受体GluK2亚基可与NETO2、GRIP蛋白相互作用改变通道特性和实现突触富集，并与AMPA受体交叉谈话，促进术后痛敏。为验证此假说，我们将采用PCR、免疫组化、免疫印迹、免疫共沉淀、钙离子成像、融合肽表达纯化和电生理等技术，研究术后① GluK2 mRNA编辑、胞浆-胞膜转运和突触靶向的变化；②GluK2-NETO2、GluK2-GRIP相互作用对KA受体通道特性、转运和突触靶向的影响；③KA受体与AMPA受体的交叉谈话机制。该项目将揭示术后疼痛的新机制，发现新的镇痛靶点。

The intrathecal administration of classic AMPA/KA receptor antagonists has shown potent analgesic action. However, the side effects limit their clinical use. Since the selectivity of classic AMPA/KA receptor antagonists for KA receptor is much higher than that for AMPA receptor, KA receptor maybe plays a critical role in spinal nociception during incisional pain. The latest studies have demonstrated the unique functional regulations of KA receptors. It remains unclear whether the functional regulations of KA receptors are involved in pain hypersensitivity. Based on our pilot studies, we hypothesized that the interaction of KA receptor GluK2 subunits with NETO2, GRIP, through enhancing the kinetics of ion channels and synaptic targeting, and the cross-talk between KA receptor and AMPA receptor were implicated in incisional pain hypersensitivity. To test the hypothesis, by using PCR, Western blot, immunohistochemistry, immunoprecipitation, fusing protein expression and purification, and electrophysiology, we would investigate ①the GluK2 mRNA editing, trafficking and synaptic targeting; ② the effects of the interaction of GluK2-NETO2, GluK2-GRIP on GluK2 desensitization, trafficking and synaptic targeting; ③the mechanism underlying the cross-talk between KA receptor and AMPA receptor during incisional pain. Our project may reveal the new mechanisms of postoperative pain and find some new analgesic targets.