title: Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model.
abstract: BACKGROUND
  Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific.
  
  
  METHODS
  Following ELA, adult stress was induced via a single exposure (acute) or repetitive daily exposure, 1 h/day for 7 days (chronic), to water avoidance stress (WAS).
  
  
  RESULTS
  Acute WAS increased pain behaviors in all adult female rats, however, females that experienced unpredictable ELA exhibited significantly more pain behaviors compared to those exposed to predictable ELA or controls. Following chronic WAS, all adult females exhibited increased pain responses, however, an exaggerated response was observed in rats exposed to unpredictable or predictable ELA compared to controls. Similarly, in adult male rats exposure to acute or chronic WAS increased pain behaviors, however, there were no differences in pain behaviors between ELA groups.
  
  
  CONCLUSIONS
  This study highlights a novel consequence of ELA on stress-induced visceral nociception in adulthood that is sex-specific. More importantly, our study suggests that ELA not only serves as a risk factor for development of chronic pain in adulthood, but also serves as a predisposition for worsening of visceral pain following adult stress in female rats.
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Prusator
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.|VA Medical Center, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.|Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: B
authors.initials: B
authors.lastname: Greenwood-Van Meerveld
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003106:Colon / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D059265:Visceral Pain / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology
keywords: early life adversity; rodent models; sex differences; stress; visceral pain