title: Concurrent psychological stress and infectious colitis is key to sustaining enhanced peripheral sensory signaling.
abstract: BACKGROUND
  The development of postinfectious-irritable bowel syndrome is associated with psychological stress but this relationship is poorly understood. The mouse Citrobacter rodentium model enhances the postinfectious excitability of colonic nociceptors, which can be further amplified by water-avoidance stress (WAS). This study tested whether concurrent infectious colitis and chronic stress enhance and sustain nociceptor excitability more than stress after resolution of infection.
  
  
  METHODS
  Male C57 mice were gavaged with C. rodentium. WAS (1 h/day) was performed at different time-points relative to the infection. After the final session of WAS, T9-T13 colonic-projecting DRG neurons were isolated, cultured overnight and patch-clamped to assess excitability. To investigate potential mechanisms, histological damage scores and colonic cytokine production were assessed.
  
  
  RESULTS
  WAS more than 30 days after C. rodentium infection produced no greater DRG excitability than WAS in uninfected mice. However, when overlapped with chronic stress (3 sessions of WAS; 7 days before, 9 days during and 9 days after C. rodentium or sham gavage), C. rodentium significantly enhanced DRG excitability vs saline-gavaged chronically stressed mice. Bodyweights and colonic damage scores were unchanged. Both WAS and C. rodentium gavage were found to significantly alter colonic cytokines at postinfection day 30.
  
  
  CONCLUSIONS
  Chronic stress and infectious colitis combine in an additive manner to heighten and prolong the sensitivity of visceral nociceptors. The effect relies on temporal coincidence of stress and infection, does not involve substantial exacerbation of inflammation, and may involve combined direct stress hormone and immune signaling on DRG neurons.
authors.affiliation: Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Spreadbury
authors.forename: F
authors.initials: F
authors.lastname: Ochoa-Cortes
authors.forename: C
authors.initials: C
authors.lastname: Ibeakanma
authors.forename: N
authors.initials: N
authors.lastname: Martin
authors.forename: D
authors.initials: D
authors.lastname: Hurlbut
authors.forename: S J
authors.initials: SJ
authors.lastname: Vanner
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D044082:Citrobacter rodentium; D003092:Colitis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D016207:Cytokines / Q000032:analysis; D004756:Enterobacteriaceae Infections / Q000150:complications / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*
chemical_list: D016207:Cytokines
keywords: Citrobacter rodentium; IBS; dorsal root ganglia; nociceptor; psychological stress; water-avoidance stress