Neuropathic pain is caused by damage or disease happened to somatosensory nerve system. Due to the high prevalence and inefficient clinic intervention, neuropathic pain has brought considerable burden for world health care system. It is urgent to find novel targets for neuropathic pain basic research and clinical management. In this study, we found that miR-22-3p was decreased in (Chronic Constriction Injury) CCI rats and involved in neuropathic pain progression. Furthermore, it was found that ENO1 was a downstream target of miR-22-3p by using bioinformatics analysis and luciferase reporter assays. MiR-22-3p downregulation promoted neuropathic pain via regulating inflammation factors expression by targeting ENO1. Then, we explored the upstream regulator of miR-22-3p by using Miranda database. It was found that circular RNA ZNF609 sponged miR-22-3p by biotinylated RNA pull-down, AGO2-RIP, and luciferase reporter assays. Collectively, our study revealed that circZNF609 promoted inflammation factors expression to aggravate neuropathic pain progression via miR-22-3p/ENO1 axis in CCI rat models. Our study might provide a new direction for neuropathic pain basic research.