Elevated Peritoneal Expression and Estrogen Regulation of Nociceptive Ion Channels in Endometriosis

<jats:sec> <jats:title>Context:</jats:title> <jats:p>Ovarian suppression is a common treatment for endometriosis-associated pelvic pain. Its exact mechanism of action is poorly understood, although it is assumed to reflect reduced production/action of estrogens.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p>The objective of the study was to measure the expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis and to investigate whether estrogens alter nociceptive gene expression in human sensory neurons.</jats:p> </jats:sec> <jats:sec> <jats:title>Design:</jats:title> <jats:p>The study was performed using human tissue analysis and cell culture.</jats:p> </jats:sec> <jats:sec> <jats:title>Setting:</jats:title> <jats:p>The study was conducted at a university research institute.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients:</jats:title> <jats:p>Peritoneal biopsies were obtained from women with CPP and endometriosis (n = 12), CPP and no endometriosis (n = 10), and no pain or endometriosis (n = 5). Endometriosis lesions were obtained from women with endometriosis (n = 18).</jats:p> </jats:sec> <jats:sec> <jats:title>Main Outcome Measures:</jats:title> <jats:p>mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in human tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P &lt; .001, P &lt; .01). TRPV1, SCN9A, and TAC1 were elevated in endometriosis lesions (P &lt; .05). P2RX3 mRNA was increased in the peritoneum of women with CPP, with and without endometriosis (P &lt; .05). Incubation of sensory neurons with 17β-estradiol increased TRPV1 mRNA (P &lt; .01). The estrogen receptor-β-selective agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile increased concentrations of TRPV1, P2RX3, SCN9A, and TAC1 mRNAs.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Estrogen-dependent expression of TRPV1 in sensory neurons may explain why ovarian suppression can reduce endometriosis-associated pain. Strategies directly targeting ion channels may offer an alternative option for the management of CPP.</jats:p> </jats:sec>