神经肽Apelin是G蛋白偶联受体APJ的内源性配体，广泛分布于中枢神经系统和外周组织，参与多种生理和病理生理过程的调节。前期工作发现脊髓水平Apelin-13在醋酸引起的内脏痛和热甩尾急性痛模型中发挥调节作用。预实验表明鞘内注射Apelin-13在慢性炎症痛模型中引起痛敏反应，但其作用机制不清楚。本项目拟用固相法合成Apelin，建立完全弗氏佐剂诱导的小鼠慢性炎症痛模型，鞘内注射Apelin及拮抗剂/抑制剂，通过痛觉行为学测试探究Apelin对慢性炎症痛的调节作用；同时用免疫荧光双标记、激光共聚焦、膜片钳、Western印迹等方法研究Apelin/APJ在脊髓背角是否通过PKC/Ras/Raf/MEK/ERK1/2信号转导通路调节NMDA受体介导的痛觉突触传递，揭示Apelin/APJ对慢性炎症痛调节的分子机制。研究结果可为潜在镇痛药物靶点Apelin/APJ系统的临床应用提供理论依据。

The neuropeptide apelin is the endogenous ligand for APJ, a G protein-coupled receptor (GPCR). Apelin/APJ system is widely distributed in central nervous system and peripheral tissues, and involved in a broad range of physiological and pathophysiological processes. Our previous reports demonstrate that apelin-13 has played a role in regulating acetic acid-induced visceral pain and acute pain (tail-flick test) at spinal level in mice. Our preliminary experiment shows that intrathecal (i.t.) administration of apelin-13 induced hyperalgesia in the chronic inflammatory pain mouse model. However, its mechanism is still unknown. The present proposal is designed to synthesize apelin using solid-phase synthesis method and establish a mouse model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA). Mice will be i.t. injected with apelin and antagonists/inhibitors, and the pain-related behavior will be evaluated to study the regulatory effect of apelin on chronic inflammatory pain. Whether the effect of apelin/APJ on NMDA receptor-mediated synaptic transmission is through the PKC/Ras/Raf/MEK/ERK1/2 signal transduction pathway in the spinal dorsal horn will be investigated, using methods such as dual-immunofluorescence, confocal laser scanning microscope (CLSM), patch-clamp recording technique, western blot, etc. The molecular mechanism of apelin/APJ on the chronic inflammatory pain will be indicated. The results could provide theoretical basis for the clinical application of apelin/APJ system, a potential analgesic drug target.