【Abstract】Objective To investigate the role of dorsal root ganglion (DRG) neuron P2X3 receptors in the development and progression of neuropathic pain (NP) rats and analyze its relationship with phosphorylated mitogen activated protein kinase p38 (p38 MAPK). Methods Sixty rats were randomly divided into sham operation group, model group, P2X3 receptor antagonist group, P2X3 receptor agonist group. The model of NP rats was established by the method of sciatic nerve constriction injury. 14 rats in the sham operation group and 12 rats in the model group were injected with 20 μL sterile saline. Twelve rats in the P2X3 receptor antagonist group were injected intrathecally with 10 μL of sterile normal saline+10 μL of A317491, and thirteen rats in the P2X3 receptor agonist group were injected intrathecally with 10 μL of sterile saline+10 μL of ATP. The paw withdraw thermal latency (PWTL) and mechanical withdraw threshold(MWT) of each group of rats were evaluated before and after operation. The expressions of P2X3 receptor and pp38MAPK protein in DRG7 and 14 days after operation were detected. The correlation between P2X3 receptor and pp38MAPK was analyzed by Pearson correlation coefficient. ResultsIn the model group, there were obvious signs of hyperalgesia in the affected limbs, and P2X3 receptor agonist group was more serious, and P2X3 receptor antagonist group was improved. In model group, P2X3 receptor antagonist group and P2X3 receptor agonist group, one day after operation was shorter than that before operation, and 1~14 days after operation remained stable (P＜005). Compared with the model group, the PWTL of P2X3 receptor antagonist group was prolonged and P2X3 receptor agonist group was shortened at 1~14 days after operation, but the three groups were still shorter than the sham operation group (P＜005). The MWT decreased in model group, P2X3 receptor antagonist group and P2X3 receptor agonist group at 1 day after operation, and decreased to the lowest level at 10 dayss, 10 days and 7 days after operation respectively (P＜005). Compared with the model group, MWT of P2X3 receptor antagonist group increased and MWT of P2X3 receptor agonist decreased 1~14 days after operation, while the three groups were still lower than those of the sham operation group (P＜005) Compared with the model group, the relative expressions of P2X3 receptor and pp38MAPK protein in DRG of P2X3 receptor antagonist group decreased on 7 and 14 days after operation, while those of P2X3 receptor agonist group increased, but the three groups were higher than those of sham operation group (P＜005). According to Pearson correlation analysis, the relative expression of P2X3 receptor was positively correlated with the relative expression of pp38MAPK protein (P＜0001). Conclusion DRG neuron P2X3 receptor activation is involved in promoting the occurrence and progression of disease in NP rats, and P2X3 receptor activation can promote the increase of p38 MAPK phosphorylation. P2X3 receptor is positively correlated with pp38 MAPK.