Involvement of bradykinin and bradykinin B1 receptor in patients with endometriosis

Endometriosis (EM), a benign aseptic inflammatory disease, is associated with the presence of endometrial foci. Pain, one of its typical symptoms, has been reported as a constant stressor, but the etiology and pathogenesis of EM-associated pain are unclear. In the present study, eutopic and ectopic endometrium samples from women with EM (n=50) and normal endometrium samples from control subjects (n=20) were collected. Serum levels of prostaglandin [E.sub.2] ([PGE.sub.2]), prostaglandin F2[alpha] (PGF2[alpha]) and bradykinin (BK) were measured using commercial ELISA kits. The expression of the BKB1 receptor (BKB1R) protein was evaluated by immunohistochemical staining and western blot assay. The mRNA expression of BKB1R was measured by reverse transcription-quantitative PCR. The results revealed that there was a substantial increase in the protein and mRNA expression of BKB1R, as well as the release of [PGE.sub.2], PGF2[alpha] and BK in the blood, in the EM group compared with that in the control group. Moreover, [PGE.sub.2], PGF2[alpha] and BK levels were significantly correlated with each other, as well as with the pain intensity of EM. The increased expression levels of BKB1R protein and mRNA were positively correlated with the pain degree of EM. Thus, these data indicated that BK and BKB1R were involved in the pathological onset of EM-associated pain and that they may play an important role in EM-related pain by inducing [PGE.sub.2] and PGF2[alpha]. The data indicate a potential new therapeutic target for EM-related pain. Key words: endometriosis, bradykinin, bradykinin B1 receptor, prostaglandin [E.sub.2], prostaglandin F2[alpha], pain