title: Brain-gut interactions increase peripheral nociceptive signaling in mice with postinfectious irritable bowel syndrome.
abstract: OBJECTIVE
  To investigate the peripheral sensory effects of repeated stress in patients with postinfectious irritable bowel syndrome (IBS), we tested whether stress following self-limiting bacterial colitis increases colonic dorsal root ganglia (DRG) nociceptive signaling.
  
  
  METHODS
  C57BL/6 mice were infected with Citrobacter rodentium. Stress was induced using a 9-day water avoidance paradigm (days 21-30 after infection). Colonic DRG neuronal excitability was measured using perforated patch clamp techniques, in vitro multi-unit afferent recordings, and measurements of visceromotor reflexes.
  
  
  RESULTS
  Combined stress and prior infection increased corticosterone and epinephrine levels, compared with infected animals, but did not alter the resolution of colonic inflammation. These changes were associated with increased neuronal excitability and parallel changes in multi-unit afferent recordings and visceromotor reflex thresholds. Protease activity was increased at day 30 following infection with C rodentium. Protease inhibitors markedly reduced the effects of colonic supernatants on neuronal excitability from C rodentium but not stressed animals. Colonic DRG neurons expressed messenger RNAs for the β(2) adrenergic and glucocorticoid receptors; incubation with stress mediators recapitulated the effects on neuronal excitability observed with chronic stress alone. PAR2 activation with concentrations of the activating peptide SLIGRL that had no effect on neuronal excitability in controls caused marked increases in excitability when applied to neurons from chronically stressed animals.
  
  
  CONCLUSIONS
  Stress, combined with prior acute colitis, results in exaggerated peripheral nociceptive signaling. Proteases and stress mediators can signal directly to colonic DRG neurons; further analysis of these pathways could provide new targets for treatment of patients with postinfectious IBS.
authors.affiliation: Gastrointestinal Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Ibeakanma
authors.forename: Fernando
authors.initials: F
authors.lastname: Ochoa-Cortes
authors.forename: Marcela
authors.initials: M
authors.lastname: Miranda-Morales
authors.forename: Todd
authors.initials: T
authors.lastname: McDonald
authors.forename: Ian
authors.initials: I
authors.lastname: Spreadbury
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cenac
authors.forename: Fiore
authors.initials: F
authors.lastname: Cattaruzza
authors.forename: David
authors.initials: D
authors.lastname: Hurlbut
authors.forename: Stephanie
authors.initials: S
authors.lastname: Vanner
authors.forename: Nigel
authors.initials: N
authors.lastname: Bunnett
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.forename: Stephen
authors.initials: S
authors.lastname: Vanner
mesh_terms: D000200:Action Potentials; D000818:Animals; D044082:Citrobacter rodentium; D003092:Colitis / Q000150:complications*; D003106:Colon / Q000201:enzymology; D003345:Corticosterone / Q000097:blood; D004756:Enterobacteriaceae Infections / Q000201:enzymology / Q000382:microbiology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000097:blood; D005727:Ganglia, Spinal / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000201:enzymology / Q000382:microbiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010447:Peptide Hydrolases / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*
chemical_list: D010447:Peptide Hydrolases; D003345:Corticosterone; D004837:Epinephrine