Inhibition of TRPM3 by Primidone Provides a Potential Therapeutic Method for Adenomyosis Management

Zhixing Jin,1,* Yaoming Peng,2,* He Zhang,1 Xiaoping He,2 Yi Zhang,1 Xin Pan,1 Min Li,1 Qianqian Yang3 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 2Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of China; 3Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Li, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215123, People’s Republic of China, Email [email protected] Qianqian Yang, Department of Pathology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215123, Jiangsu, People’s Republic of China, Email [email protected]: To test the expression profile of transient receptor potential channels (TRPs) in adenomyosis patients and evaluate the effects of primidone on tamoxifen-induced adenomyosis mice.Patients and Methods: This study included in vivo animal model and human tissue samples. Eutopic endometrium from adenomyosis patients (n=20) was collected and subjected to mRNA analysis of TRP channels. TRPA1, TRPV1 and TRPM3 in adenomyosis patients (n=50) and tamoxifen-induced adenomyosis mice (n=6) were examined by immunohistochemistry. From 10 weeks after birth, primidone (2 mg/kg/d) and atosiban (1 mg/kg/d) were given separately to adenomyotic mice by intraperitoneal injection for 3 weeks. The hotplate test was conducted once a week beginning at 10 weeks, and then uterine samples were harvested for HE staining and RNA-seq at 13 weeks.Results: The mRNA expression of 15 TRPs was significantly increased in the proliferative phase of the adenomyotic endometrium. TRPV1, TRPM3 or TRPA1 staining levels were positively correlated with dysmenorrhea severity, menses amount and uterine size. In tamoxifen-induced adenomyosis mice, primidone had a significant effect on both the depth of myometrial infiltration and analgesia. Forty-seven DEGSSs were identifieSd after primidone treatment, and bioinformatics analysis predicted that they were enriched in the cell cycle and cell division.Conclusion: The expression profile of TRP channels varies significantly in adenomyosis patients, and primidone may provide a potential therapeutic method for adenomyosis management.Keywords: adenomyosis, TRPs, primidone, pelvic pain, TRPM3