瑞芬太尼痛觉过敏临床常见，其机制尚不明确。课题组前期工作(发表于Anesthesiology)证实术后kalirin-7调节突触形成与瑞芬太尼痛敏密切相关。新近研究发现Neuroligin-1/Neurexin-1α是谷氨酸能兴奋性神经突触重塑的关键，故推测Neuroligin-1/Neurexin-1α—Kalirin-7通路可能是介导瑞芬太尼痛敏的重要机制。本研究拟建立在体SD大鼠瑞芬太尼痛敏模型，利用痛敏行为学测定、Western blot、共沉淀、荧光和高尔基染色研究Neuroligin-1、Neurexin-1α、Kalirin-7和树突棘形态在瑞芬太尼痛敏中的动态变化；体外培养大鼠脊髓背角神经元，应用Neuroligin-1-siRNA转染技术研究突触重塑分子机制在瑞芬太尼痛敏中的调控作用。本研究将为瑞芬太尼痛敏现象的临床防治提供新思路。

Remifentanil-induced hyperalgesia seems more frequently and predictably when compared with other opioids, but its mechanism remains elusive. Our previous study has published in Anesthesiology and manifested that postoperative kalirin-7 mediated synaptogenesis is involved in remifentanil-induced hyperalgesia. Recent studies have reported that Neuroligin-1/Neurexin-1α is critical for central glutaminergic excitatory synapsic plasticity. We hypothesize that Neuroligin-1/Neurexin-1α—Kalirin-7 pathway may exert a pivotal effect on remifentanil-induced hyperalgesia. Therefore in this study, following accomplishment of a rat model of remifentanil-induced postoperative hyperalgesia, we use nociceptive behavior test, Western blot, coimmunoprecipitation, immunofluorescence and Golgi staining to detect dynamic changes of Neuroligin-1、Neurexin-1α、Kalirin-7 and dendritic spines morphology in remifentanil-induced hyperalgesia. We also culture rat primary spinal dorsal horn neurons, and employ Neuroligin-1-siRNA to demonstrate the molecular pathogenesis of synaptic plasticity in remifentanil-induced hyperalgesia. The present study will provide the novel options for the effective prevention of hyperalgesia induced by remifentanil in clinics.