Role of Brain-Derived Neurotrophic Factor in Endometriosis Pain.

Abstract

Brain-derived neurotrophic factor (BDNF) is a regulator for the formation and maintenance of chronic pain in various chronic disorders and has been shown to increase in the serum of women with endometriosis. However, BDNF expression in the peritoneal fluid (PF) and ectopic lesions and its role in endometriosis pain remain unclear. Thus, this study aims to determine the BDNF concentrations in serum and PFs and BDNF expression levels in ectopic lesions and endometriotic stromal cells (ESCs) of women with endometriosis (n = 60). The obtained results were then compared with those of women without endometriosis (n = 38). Brain-derived neurotrophic factor concentrations in serum and PF, as well as the BDNF expression levels in ectopic lesions and endometriotic cells, were evaluated through enzyme-linked immunosorbent assay, immunohistochemical staining, quantitative real-time polymerase chain reaction, and Western blot analysis. As a result, BDNF concentrations in serum and PF were significantly higher in women with endometriosis with pain (2284.3 ± 51.5 pg/mL, n = 23; 58.8 ± 6.4 pg/mL, n = 16) than in women with endometriosis without pain (1999.8 ± 61.1 pg/mL, n = 37; 31.7 ± 2.9 pg/mL, n = 25; P < .01). Moreover, BDNF messenger RNA (mRNA) expression levels in ectopic lesions (8.97 ± 1.44, n = 29) were significantly higher than eutopic (0.97 ± 0.14, n = 16; P < .01) and control endometrium (1.23 ± 0.19, n = 18; P < .01) and were correlated with endometriosis pain ( P < .05). Furthermore, increased BDNF mRNA and protein expression levels in ESCs induced by estradiol or interleukin 1β were removed using a phosphorylated extracellular-regulated protein kinase 1/2 inhibitor. These results suggest that BDNF may play an important role in the pathogenesis of endometriosis pain.