慢性疼痛临床诊疗效果不佳，疼痛慢性化机制不明确、缺乏特异性干预手段是关键限制性难题。神经元兴奋性异常是其特征表现，但调控机制尚不清楚。既往报道慢性疼痛伴随胶质细胞激活和Kir4.1钾离子通道表达下降，本团队进一步发现，条件性敲除胶质细胞Kir4.1可致小鼠痛阈下降，嘌呤受体拮抗剂可显著逆转该表现；干扰非电压依赖钠离子漏电流通道(NALCN)表达可调控DRG内Kir4.1表达水平，并减轻其痛觉敏感性。因此，我们推测胶质细胞Kir4.1钾离子通道下调及嘌呤信号途径改变是介导神经元兴奋性异常和慢性疼痛的重要机制，而神经损伤早期NALCN通道表达水平上调是疼痛慢性化关键启动因子。本研究拟采用基因表达调控，信号通路干预等手段，通过行为学、分子生物学、电生理学等实验，探讨Kir4.1通道在慢性疼痛中的作用及机制，以期为阐释慢性疼痛发病机制及临床诊疗提供新的依据。

The mechanism of chronic pain is unclear, and the effect of conventional analgesics is poor. Neuronal excitability plays an important role, but its regulation mechanism is still unclear. Previous studies have reported that chronic pain is accompanied by glial cell activation and decreased expression of Kir4.1 potassium channel. We further found that the conditioned knockout of glial cell Kir4.1 can cause decreased pain threshold in mice. In addition, intrathecal injection P2 blocker PPADS can decrease the mechanical pain after CCI. Furthermore, using AAV-NALCN-shRNA can also decrease the expression of Kir4.1 and the mechanic pain. Therefore, we hypothesized that increased NALCN can down-regulate Kir4.1 in glial cells, which mediated neuronal excitatory abnormalities by purine signaling and participated in the pathogenesis of chronic pain. This study intends to explore the mechanism of Kir4.1 in chronic pain through behavioral, molecular biology, electrophysiology and other experiments, using conditioned gene knockout, signal pathway intervention and other means. In order to provide new insight for pathogenesis and new target and method for intervention of chronic pain.