Resveratrol Reduces Myometrial Infiltration, Uterine Hyperactivity, and Stress Levels and Alleviates Generalized Hyperalgesia in Mice With Induced Adenomyosis

In this study, we sought to determine whether resveratrol (RSV), a nonhormonal compound, would suppress the myometrial infiltration, improve pain behavior, lower stress level, improve the expression of some proteins known to be involved in adenomyosis, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 28 female ICR mice neonatally dosed with tamoxifen, while another 12 (group C) were dosed with solvent only, serving as a blank control. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 3 groups: low-dose RSV (2 mg/kg), high-dose RSV (3 mg/kg), and untreated. Group C received no treatment. After 3 weeks of treatment, they were hotplate tested again, their uterine horns and brains were harvested, and a blood sample was taken to measure the plasma corticosterone (CORT) level by enzyme-linked immunosorbent assay. The left uterine horn was used for immunohistochemistry analysis. The brain stem nucleus raphe magnus (NRM) sections were subjected to immunofluorescence staining for glutamic acid decarboxylase isoform 65 (GAD65). The depth of myometrial infiltration and uterine contractility was evaluated. We found that RSV is well tolerated and that it dose dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility and lowered plasma CORT levels, and improved the expression of some proteins known to be involved in adenomyosis. It also elevated the number of GAD65-expressing neurons in the brain stem NRM, possibly boosting the GABAergic inhibition of pain due to adenomyosis. Therefore, RSV appears to be a promising compound for treating adenomyosis.