瑞芬太尼诱发的痛觉过敏（RIH）临床常见，尚无可靠治疗方法。课题组前期工作（发表于Anesthesiology和A&A等）证实NMDA受体NR2B trafficking在RIH中发挥重要调控作用，但其下游机制尚未明确。新近文献证实NR2B可调控CaMKⅡα磷酸化水平，参与脊髓LTP形成与维持。HDAC4胞核和胞浆shuttling在突触可塑性及疼痛记忆中发挥重要作用，且受NMDAR和CaMKⅡα调控。本研究拟建立在体大鼠瑞芬太尼痛觉过敏模型，利用疼痛行为学、western blot、免疫荧光、共沉淀、免疫电镜和高尔基染色等方法探讨NR2B、CaMKⅡα、HDAC4及树突棘形态在RIH中的动态变化；进一步培养大鼠脊髓背角神经元，建立离体RIH模型，利用全细胞膜片钳等技术，研究NR2B-CaMKⅡα-HDAC4 通路在RIH中的调控机制。本研究将为瑞芬太尼痛觉过敏的临床防治提供新思路。

Remifentanil-induced hyperalgesia(RIH) is quite common in the clinic, however, there is no effective therapy at present. Our previous studies (published in 《Anesthesiology》and《A&A》) have manifested that NMDA receptor -NR2B subunit trafficking play an important role in the maintenance of remifentanil induced hyperalgesia, but its downstream remains elusive. Recent studies have supported that NR2B subunits are involved in spinal LTP development and maintenance through modulating phosphorylation of CaMKⅡα. HDAC4 shuttling between the nucleus and cytoplasm is critical for synaptic plasticity and pain memory, also regulated by NMDA receptor and CaMKⅡα. Therefore in this study, After performing a rat model of remifentanil-induced hyperalgesia, we use nociceptive behavior test, Western blot, immunofluorescence, immunoelectron microscopy, co-immunoprecipitation, and Golgi staining to detect dynamic changes of NR2B、CaMKⅡα、HDAC4 and dendritic spines structure in remifentanil-induced hyperalgesia. In vitro study, we also culture rat primary spinal dorsal horn neurons, perform RIH model in vitro, and use whole cell patch clamp method to demonstrate the role of NR2B-CaMKⅡα-HDAC4 shuttling in remifentanil-induced hyperalgesia. The present study will provide the novel options for the prevention of remifentanil induced hyperalgesia in clinics.