Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis

Erin Greaves, Kelsey Grieve, Andrew W. Horne, Philippa T. K. Saunders

Research output: Contribution to journalArticlepeer-review


Context: 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. Objective: To measure expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis; to investigate whether estrogens alter nociceptive gene expression in human sensory neurons. Design: Human tissue analysis and cell culture. Setting: University Research Institute Patients: Peritoneal biopsies were obtained from women with CPP and endometriosis (n=12), CPP and no endometriosis (n=10), and with no pain or endometriosis (n=5). Endometriosis lesions were obtained from women with endometriosis (n=18). Main outcome measures: mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens. Results: TRPV1, TRPA1 and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (p<0.001, p<0.01). TPRV1, SCN9A and TAC1 were elevated in endometriosis lesions (p<0.05). P2RX3 mRNA was increased in the peritoneum of women with CPP, with and without endometriosis (p<0.05). Incubation of sensory neurons with E2 increased TRPV1 mRNA (p<0.01); the ERβ-selective agonist DPN increased concentrations of TRPV1, P2RX3, SCN9A and TAC1 mRNAs. Conclusions: 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 management of CPP.

Original languageEnglish
Pages (from-to)jc20142282
JournalJournal of Clinical Endocrinology & Metabolism
Issue number9
Early online date16 Jul 2014
Publication statusPublished - Sep 2014


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