Endometriosis is a gynecological and painful condition affecting women of reproductive age. It is characterized by dysfunctional endometrium-like implants outside of uterine.The purpose of this study was to investigate the effect of Paeoniflorin on pain relief and explore its mechanism in alleviating pain. Methods：An animal model of endometriosis (EM) was established in rats through autologous transplantation. The rats were divided into six groups: blank group, sham group, EMS group, Paeoniflorin low-dose group, Paeoniflorin high-dose group and positive control group. The rats received treatment for weeks. The thermal radiation and mechanical pain thresholds were measured every 7 days. The recovery rate of estrus period,ovarian index, uterine index were assessed. HE staining was utilized to observe pathological changes and serum levels of GSH, SOD, ROS, PGE2, IL-6, and TGF-αwere measured using ELISA. The expression levels of TRPV1, JAK2, STAT3 in the endometrium and endometriotic lesions were measured using WB and qPCR. Results：The model group exhibited degeneration and necrosis of endometrial epithelial cells, along with inflammatory cell infiltration. Treatment with Paeoniflorin and danazol mitigated these pathological changes, leading to a decrease in ROS and an increase in SOD, CAT, and GSH. Among the groups, the high-dose Paeoniflorin group demonstrated the most significant efficacy in alleviating pain. Paeoniflorin decreased the expression of TRPV1, p-TRPV1 and JAK2. Conclusions：Paeoniflorin demonstrates the potential to inhibit the progression of endometriosis and alleviate pain. These effects may be achieved by reducing the inflammatory response and impacting the STAT3 signaling pathway in ectopic tissues.
