title: Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis.
abstract: BACKGROUND
  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
  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.
  
  
  METHODS
  The study was performed using human tissue analysis and cell culture.
  
  
  METHODS
  The study was conducted at a university research institute.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P < .001, P < .01). TRPV1, SCN9A, and TAC1 were elevated in endometriosis lesions (P < .05). P2RX3 mRNA was increased in the peritoneum of women with CPP, with and without endometriosis (P < .05). Incubation of sensory neurons with 17β-estradiol increased TRPV1 mRNA (P < .01). The estrogen receptor-β-selective agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile 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 the management of CPP.
authors.affiliation: Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queens Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Erin
authors.initials: E
authors.lastname: Greaves
authors.forename: Kelsey
authors.initials: K
authors.lastname: Grieve
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
mesh_terms: D001706:Biopsy; D015220:Calcium Channels / Q000235:genetics; D002478:Cells, Cultured; D059350:Chronic Pain / Q000209:etiology / Q000628:therapy; D053595:Embryonic Stem Cells / Q000166:cytology; D004715:Endometriosis / Q000150:complications / Q000473:pathology / Q000628:therapy*; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009619:Nociceptors / Q000378:metabolism*; D010053:Ovary / Q000502:physiology; D017699:Pelvic Pain / Q000209:etiology / Q000628:therapy*; D010537:Peritoneum / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D058477:Receptors, Purinergic P2X3 / Q000235:genetics; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics; D015320:Tachykinins / Q000235:genetics; D050051:Transient Receptor Potential Channels / Q000235:genetics
chemical_list: D015220:Calcium Channels; D004967:Estrogens; D007473:Ion Channels; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C546407:P2RX3 protein, human; D012333:RNA, Messenger; D058477:Receptors, Purinergic P2X3; C491886:SCN11A protein, human; C486866:SCN9A protein, human; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D015320:Tachykinins; D050051:Transient Receptor Potential Channels