title: Estradiol modulates visceral hyperalgesia by increasing thoracolumbar spinal GluN2B subunit activity in female rats.
abstract: BACKGROUND
  We previously reported estrogen modulates spinal N-methyl-d-aspartate (NMDA) receptor processing of colorectal pain through changes in spinal GluN1 subunit phosphorylation/expression. The purpose of this study was to investigate whether spinal GluN2B containing NMDA receptors are involved in estrogen modulation of visceral pain processing.
  
  
  METHODS
  Behavioral, molecular, and immunocytochemical techniques were used to determine spinal GluN2B expression/phosphorylation and function 48 h following subcutaneous injection of estradiol (E2) or vehicle (safflower oil, Saff oil) in ovariectomized rats in the absence or presence of colonic inflammation induced by mustard oil.
  
  
  RESULTS
  E2 increased the magnitude of the visceromotor response (VMR) to colorectal distention compared to Saff oil in non-inflamed rats. Intrathecal injection of the GluN2B subunit antagonist, Ro 25-6981, had no effect on the VMR in non-inflamed E2 or Saff oil rats. Colonic inflammation induced visceral hyperalgesia in E2, but not Saff oil rats. Visceral hyperalgesia in E2 rats was blocked by intrathecal GluN2B subunit selective antagonists. In inflamed rats, E2 increased GluN2B protein and gene expression in the thoracolumbar (TL), but not lumbosacral (LS), dorsal spinal cord. Immunocytochemical labeling showed a significant increase in GluN2B subunit in the superficial dorsal horn of E2 rats compared to Saff oil rats.
  
  
  CONCLUSIONS
  These data support the hypothesis that estrogen increases spinal processing of colonic inflammation-induced visceral hyperalgesia by increasing NMDA receptor activity. Specifically, an increase in the activity of GluN2B containing NMDA receptors in the TL spinal cord by estrogen underlies visceral hypersensitivity in the presence of colonic inflammation.
authors: Department of Neural and Pain Sciences, University of Maryland School of Dentistry, UM Center to Advance Chronic Pain Research, Baltimore, MD, USA.
authors: Y
authors: Y
authors: Ji
authors: Department of Neural and Pain Sciences, University of Maryland School of Dentistry, UM Center to Advance Chronic Pain Research, Baltimore, MD, USA.
authors: G
authors: G
authors: Bai
authors: Department of Neural and Pain Sciences, University of Maryland School of Dentistry, UM Center to Advance Chronic Pain Research, Baltimore, MD, USA.
authors: D-Y
authors: DY
authors: Cao
authors: Department of Neural and Pain Sciences, University of Maryland School of Dentistry, UM Center to Advance Chronic Pain Research, Baltimore, MD, USA.
authors: R J
authors: RJ
authors: Traub
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D008159:Lumbar Vertebrae; D009149:Mustard Plant; D010052:Ovariectomy; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D010938:Plant Oils; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013904:Thoracic Vertebrae; D059265:Visceral Pain / Q000209:etiology / Q000378:metabolism*
chemical_list: D004967:Estrogens; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D010938:Plant Oils; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D004958:Estradiol; C027793:mustard oil
keywords: NMDA receptor; estradiol; gonadal hormones; pain; spinal cord; visceral nociception