CaMKII-NMDA受体通路在瑞芬太尼诱导痛觉过敏中的作用及细胞通透性融合肽的干预研究

Remifentanil-induced hyperalgesia in clinical anesthesia can lead to some adverse events such as postoperative agitation, which maybe affect the control of pain in surgical patients. The mechanism of remifentanil-induced hyperalgesia maybe connect with the activation of CaMKII-NMDA receptor in the central nervous system. This study will establish the rat model of incisional pain under different anesthesia, make use of behavior test, western blot, immumoflurescence and co-immunoprecipitation, and measure the concentration of intracellular calcium, glutamic acid and aspartic acid using microdialysis and RP-HPLC. And then we will study the effect of remifentanil on the phosphorylation level of CaMKII subtypes (alpha and beta) and NR2B subunit in NMDA receptors on the pain pathways. We will also investigate the detailed mechanisms which traditional sodium channel blockers (lidocaine) and NMDA receptor antagonists (ketamine) inhibit opioid-induced hyperalgesia. At the same time we will explore the feasibility of cell-permeable fusion peptide for treatment of remifentanyl-induced hyperalgesia. Our study will provide a theoretical basis for clinical anesthesia.

瑞芬太尼诱导的痛觉过敏在临床麻醉中可导致术后躁动等不良事件，对控制手术患者近远期疼痛具有不利影响。其机制可能与阿片类药物对中枢神经系统CaMKII-NMDA受体伤害反应系统的激活有关。本研究拟通过建立不同麻醉方案下的大鼠切口痛模型，运用行为学，蛋白免疫印迹、免疫荧光和免疫共沉淀等方法，结合微透析和反相高效液相测定谷氨酸及天冬氨酸含量，测定细胞内钙浓度，深入研究瑞芬太尼对痛觉传导通路上不同部位的CaMKIIα、β亚型和NMDA受体疼痛信号传导相关的功能调节亚基NR2B磷酸化水平的变化；同时研究临床上常用的传统钠通道阻滞剂利多卡因和NMDA受体拮抗剂氯胺酮在抑制阿片类药物诱导痛觉过敏的机制上有何异同，并探讨细胞通透性融合肽防治瑞芬太尼诱导痛觉过敏的可行性，为临床实践提供理论依据。

瑞芬太尼诱导的痛觉过敏在临床麻醉中可导致术后躁动等不良事件，对控制手术患者近远期疼痛具有不利影响。其机制可能与阿片类药物对中枢神经系统 CaMKII-NMDA 受体伤害反应系统的激活有关。本研究拟通过建立不同麻醉方案下的大鼠切口痛模型，运用行为学，蛋白免疫印迹、免疫荧光和免疫共沉淀等方法，结合微透析和反相高效液相测定谷氨酸及天冬氨酸含量，测定细胞内钙浓度，深入研究瑞芬太尼对痛觉传导通路上不同部位的CaMKIIα 、β 亚型和 NMDA 受体疼痛信号传导相关的功能调节亚基 NR2B 磷酸化水平的变化； 同时研究临床上常用的传统钠通道阻滞剂利多卡因和 NMDA 受体拮抗剂氯胺酮在抑制阿片类药物诱导痛觉过敏的机制上有何异同，并探讨细胞通透性融合肽防治瑞芬太尼诱导痛觉过敏的可行性，为临床实践提供理论依据。