title: Release of endogenous opioids during a chronic IBD model suppresses the excitability of colonic DRG neurons.
abstract: BACKGROUND
  Endogenous opioids are implicated in pain-regulation in chronic inflammatory bowel disease (IBD). We sought to examine whether endogenous opioids suppress the excitability of colonic nociceptive dorsal root ganglia (DRG) neurons during chronic IBD, and if so, whether modulation of underlying voltage-gated K(+) currents was involved.
  
  
  METHODS
  The effects of chronic dextran sulfate sodium (DSS) colitis on afferent signaling in mice was studied using patch clamp recordings. Colonic DRG neurons were identified using Fast Blue retrograde labeling and recordings obtained from small DRG neurons (<40 pF).
  
  
  RESULTS
  In current-clamp recordings, the rheobase of neurons was increased 47% (P < 0.01) and action potential discharge at twice rheobase decreased 23% (P < 0.05) following incubation in colonic supernatants from chronic DSS mice. β-endorphin increased 14-fold, and tissue opioid immunoreactivity and expression in CD4+ cells observed by flow cytometry increased in chronic DSS colons. Incubation of naïve neurons in the μ-opioid receptor agonist D-Ala(2), N- MePhe(4), Gly-ol (DAMGO) (10 nM) partially recapitulated the effects of supernatants from DSS mice on rheobase. Supernatant effects were blocked by the μ-opioid receptor antagonist naloxone. In voltage clamp, chronic DSS supernatants and DAMGO increased I(A) K(+) currents.
  
  
  CONCLUSIONS
  The release of endogenous opioids during chronic inflammation in mice suppresses the excitability of nociceptive DRG neurons. Targeting immune cells may provide a novel means of modulating IBD pain.
authors.affiliation: Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Valdez-Morales
authors.forename: R
authors.initials: R
authors.lastname: Guerrero-Alba
authors.forename: F
authors.initials: F
authors.lastname: Ochoa-Cortes
authors.forename: J
authors.initials: J
authors.lastname: Benson
authors.forename: I
authors.initials: I
authors.lastname: Spreadbury
authors.forename: D
authors.initials: D
authors.lastname: Hurlbut
authors.forename: M
authors.initials: M
authors.lastname: Miranda-Morales
authors.forename: A E
authors.initials: AE
authors.lastname: Lomax
authors.forename: S
authors.initials: S
authors.lastname: Vanner
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002469:Cell Separation; D002908:Chronic Disease; D003106:Colon / Q000294:innervation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D001615:beta-Endorphin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001615:beta-Endorphin