Friday, July 18, 2014

estrogen may increase nerve pain signals in endo

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

Greaves E1, Grieve K, Horne AW, Saunders PT.

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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 ERĪ²-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.

PMID: 25029427 [PubMed - as supplied by publisher]