Background Recently emerging evidence indicates that endometriotic lesions are wounds undergoing repeated tissue injury and repair (ReTIAR), and platelets induce epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), leading ultimately to fibrosis. was taken to measure the plasma corticosterone level by ELISA. The left uterine horn was used for immunohistochemistry buy ZCL-278 analysis. The brainstem nucleus raphe magnus (NRM) sections were subjected to immunofluorescence staining for GAD65. The depth of myometrial infiltration and uterine contractility were evaluated. Results We found that both Ozagrel treatment and platelet depletion dose-dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility, and lowered plasma corticosterone levels, improved the expression of some proteins known to be involved in adenomyosis and slowed down the process of fibrogenesis. It also elevated the number of GAD65-expressing neurons in the brainstem NRM, possibly boosting the GABAergic inhibition of pain due to adenomyosis. Conclusion This study further provides evidence that platelets play important roles in the development of adenomyosis. Anti-platelet treatment is efficacious in suppression of myometrial infiltration, improving generalized hyperalgesia, reducing uterine hyperactivity and systemic corticosterone levels. Collectively, these results demonstrate that anti-platelet therapy seems to be promising for treating adenomyosis. Electronic supplementary material The online version of this article (doi:10.1186/s12958-016-0198-1) contains supplementary material, which is available to authorized users. [21] and approved by the institutional experimental animals review board of Shanghai OB/GYN Hospital, Fudan University. Experimental protocol This experiment was conducted side-by-side with another experiment evaluating the efficacy of epigallocatechin-3-gallate (EGCG) in treating adenomyosis in mice, as reported in GADD45B [20]. Fifty-six buy ZCL-278 female neonatal pups were orally dosed with tamoxifen from day 2 to day 5 after birth, while another 12 were dosed in similar fashion with the solvent only (control group, or group C). Starting from 4?weeks after birth, hotplate test was administered to all mice every 4?weeks, as described previously [2, 19] (see Additional file 1 for full description). At the 16th week after birth, all mice dosed with tamoxifen were randomly divided into6 groups of roughly equal size, Group U (values of less than 0.05 were considered statistically significant. All computations were made with R statistics software system version 3.3.1 [28]. Results Consistent with Parrott et al. [17, 18] and as previously reported [2, 19], we found that adenomyosis was successfully induced in all (100?%) mice dosed with tamoxifen but none in un-dosed mice. Ozagrel was well-tolerated, as no buy ZCL-278 mice in either LO or HO group died, and we found nothing unusual in these mice. In HD group, however, 1 mouse died after it received the 4th injection of the depletion antibody, and 2 appeared to be lethargic. In the LD group, no mice died and nothing appeared unusual. There was no difference in platelet counts between the mice in groups UT, NI, LO, and HO at the end of the experiment. However, the platelet count in mice in both LD and HD groups was reduced by 99.6 and 99.7?% as compared with those in the NI group, demonstrating the effectiveness of platelet depletion in these two groups. Treatment effect on the depth of myometrial infiltration, hotplate latency, and uterine and bodyweight We first evaluated the effect of Ozagrel treatment or platelet depletion on the depth of myometrial infiltration. We found that, compared with untreated mice, mice treated with either low- or high-dose Ozagrel had significantly less infiltration (both ranging from 0.31 to 0.76; Table?1 and Fig.?5). Fig. 5 Summary of immunohistochemistry results. Boxplot of immunoreactivity against CD41 (a), the buy ZCL-278 number of F4/80+ positive macrophages (b), p-p65 c, PR-B (d), COX-2 (e), TRPV1 (f),OTR (g), myometrial OTR (h), Collagen I (i), and Collagen IV (j) in ectopic/eutopic … Fig. 6 Representative immunohistochemisty staining of markers of smooth muscle metaplasia and fibrosis in ectopic and eutopic endometrium. Different rows indicate different proteins in different groups (arranged in different columns) with different doses of … Table 1 Results from early/later platelet depletion experiment. All results were based on multiple regression analyses with the independent variable square-root transformed and dummy variables indicating the presence or absence of adenomyosis, non-immune IgG … In addition to these markers,.