P2X7受体介导的小胶质细胞NALP3炎性体活化在术后急性疼痛向慢性疼痛综合征转化中的作用探究

Surgical trauma induced acute postoperative pain is easily developed to chronic postsurgical pain syndromes(CPSP). CPSP may last for several yaers which severely affect the patient's physical and mental health, and life quality as well. Recent data and our previous studies showed that microglia in spinal dorsal horn play an important role in the transition from acute postoperative pain to CPSP, and microglia P2X7 receptor and inflammatory response participate the formation of chronic pain. Our group speculated a signaling cascade pathway, which is microglia P2X7 receptor ativation→NALP3 inflammasome activation→caspase-1→IL-1βrelease, play a key role in the transition from acute postoperative pain to CPSP. Firstly we plan to verify the signaling cascade pathway does exist in cultured microglia, and then with the techniques such as intrathecal transplatation of NALP3 inflammasome activated microglia, RNA interference and intrathecal injection of tool drugs, we try to elucidate the role of P2X7 receptor mediated microglia NALP3 inflammasome activation in the transition from acute postoperative pain to CPSP in vivo by "skin and muscle incision and retraction"model，a commomly used model of CPSP developed from acute postoperative pain.Our study could provide theoretical direction for the prevention and treatment of CPSP.

手术创伤引起的患者术后急性疼痛往往发展演变为术后慢性疼痛综合征（CPSP）。CPSP持续时间可达数年，严重影响患者的身心健康和生活质量。近年文献及课题组前期研究提示脊髓背角小胶质细胞参与术后急性痛向CPSP转化的病理生理进程；小胶质细胞P2X7受体及炎症反应参与慢性疼痛的形成。课题组推测小胶质细胞P2X7受体活化→NALP3炎性体活化→caspase-1→IL-1β释放这一信号级联通路在术后急性痛向CPSP发展演变进程中起关键作用。课题组拟首先体外培养脊髓来源小胶质细胞，在细胞水平验证上述信号通路的存在；进一步模拟"皮肤肌肉切开牵拉"这一术后急性痛转变为慢性痛的通用模型，采用鞘内移植NALP3炎性体活化后的小胶质细胞、鞘注工具药、RNA干扰等技术和方法探究脊髓背角P2X7受体介导的小胶质细胞NALP3炎性体活化在术后急性痛向CPSP转化中的作用，以期为CPSP的防治提供理论依据。

手术创伤引起的患者术后急性疼痛往往发展演变为术后慢性疼痛综合征（CPSP）。CPSP持续时间可达数年，严重影响患者的身心健康和生活质量。课题组首先在细胞水平验证P2X7受体(P2X7R)活化后可通过NALP3炎性体活化，最后引起IL-1β、TNF-α等炎性介质的释放。在此基础上，课题组模拟大鼠“皮肤肌肉切开牵拉”这一术后急性痛转变为术后慢性痛经典模型，研究证实该手术模型中虽然组织学上没有发现外周神经损伤，但模型大鼠出现了明显的机械痛敏，并表现出慢性疼痛特有的C类神经纤维长时程增强（LTP）。进一步研究显示SMIR模型大鼠手术同侧脊髓背角及背根神经节的小胶质细胞明显活化，且手术同侧脊髓背角胶质细胞活化程度、P2X7R表达量、TNF-α的表达量与痛敏程度相关；P2X7R拮抗剂BBG可以抑制SMIR模型大鼠的机械痛敏形成和TNF-α的表达增加。课题研究提示胶质细胞P2X7R介导的炎症反应在术后慢性痛的形成中发挥重要作用。