title: Sex steroids localized to the amygdala increase pain responses to visceral stimulation in rats.
abstract: Females are disproportionately affected by irritable bowel syndrome (IBS) with menstrual cycle-dependent fluctuations in abdominal pain suggesting a role for ovarian hormones. IBS patients also exhibit greater activation of brain areas involved in pain affect such as the amygdala, yet the role of supraspinal processes in the effects of ovarian hormones on visceral pain is largely unexplored. The goal of the current study was to determine whether sex steroids act at the level of the amygdala to alter colonic pain sensitivity. Ovariectomized rats received implants on the amygdala of progesterone, estradiol, progesterone combined with estradiol, or cholesterol as a control to examine the involvement of the amygdala in ovarian hormone-mediated changes in visceral sensitivity. Visceral sensitivity was quantified as the number of abdominal contractions, a visceromotor response (VMR), in response to graded pressures of colorectal distension (CRD). Somatic sensitivity was also assessed by measuring the mechanical force required to elicit hindpaw withdrawal. Elevated levels of progesterone and/or estradiol on the amygdala heightened the responsiveness to CRD; in contrast, neither estradiol nor progesterone altered somatic sensation. Furthermore, administration of progesterone or estradiol to areas adjacent to the amygdala did not affect visceral sensitivity. Future studies will address the specific steroid receptors mediating the effects of progesterone and estradiol.
  
  
  CONCLUSIONS
  To our knowledge, this study represents the first description of a specific brain site mediating the effects of ovarian steroids on visceral sensitivity. These data also suggest that an amygdala-dependent mechanism may be responsible, at least in part, for the exacerbation of visceral symptomatology in females.
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Myers
authors.forename: Jay
authors.initials: J
authors.lastname: Schulkin
authors.forename: Beverley
authors.initials: B
authors.lastname: Greenwood-Van Meerveld
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003106:Colon / Q000294:innervation*; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage*; D043183:Irritable Bowel Syndrome / Q000503:physiopathology; D010052:Ovariectomy; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D011374:Progesterone / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D014781:Viscera / Q000294:innervation
chemical_list: D012739:Gonadal Steroid Hormones; D011374:Progesterone; D004958:Estradiol