躯体感觉通路BDNF-TrκB级联与KCC2交互作用在BPA后痛觉敏化中的作用机制研究

臂丛神经根性撕脱伤（BPA）诱发的神经病理性痛（NPP）是临床的治疗难题。痛觉敏化在NPP的发生和维持过程中扮演重要角色。躯体感觉通路中BDNF-TrκB级联的激活是该通路在病理状况下做出的迅速反应；K+-Cl-离子协同转运蛋白（KCC2）在神经元胞内的表达和功能异常均可促进NPP的发生和发展。既往及我们的前期研究表明，BPA后脊髓背角活化的胶质细胞可通过BDNF-TrκB级联作用于KCC2，致神经元胞内Cl-堆积，脊髓中枢抑制作用受损，致痛觉敏化；那么，背根神经节作为感觉传入信息整合的第一站，就应该受到该级联反应的影响，与脊髓中枢相互作用，在痛觉敏化过程中占据同等重要的地位。课题组前期成功建立了新型BPA小鼠模型，拟在此基础上以躯体感觉通路上BDNF-TrκB级联作用于KCC2所导致的抑制作用丢失为核心，探讨痛觉敏化的深部机制，为未来以周围伤害性感受器为NPP的治疗靶点提供理论依据。

Brachial plexus avulsion (BPA) induced neuropathic pain (NPP) is one intractable complication in clinical work. Pain sensitization plays a crucial part in the occurrence and maintenance of NPP. The activation of BDNF-TrκB cascade on somatosensory pathway is a rapid reaction of this pathway under pathological conditions. The abnormal expression and function of KCC2, as the most important intracellular K+-Cl- ion combined transporter, can promote the occurrence and development of NPP. Previous studies showed that the glial cells activated in the spinal dorsal horn after BPA can act on KCC2 through the cascade of BDNF-TrκB, resulting in intracellular Cl- accumulation of neurons, impairing central inhibition of the spinal cord, and finally leading to pain sensitization. Then, as the first stop of the integration of somatosensory information, dorsal root ganglion should be affected by this cascade reaction in the process of pain information processing and interact with the spinal cord, which plays an equally important role in the process of pain sensitization. Our research group has successfully established a new BPA induced NPP mouse model in the early stage. On this basis, it intends to further explore the deep mechanism of pain sensitization on the somatosensory pathway based on the loss of inhibitory function caused by the cascade of BDNF-TrκB on KCC2, so as to provide theoretical basis for using peripheral nociceptors as therapeutic targets for NPP in the future.