title: Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis.
abstract: Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways.
  
  
  
  Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca2+imaging techniques.
  
  
  
  Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca2+responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits.
  
  
  
  Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD.
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.|Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, México.
authors: Raquel
authors: R
authors: Guerrero-Alba
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.|Departamento de Cirugía, Centro de Ciencias Biomédicas, Universidad Autónoma de Aguascalientes, Cátedras CONACYT, Aguascalientes México.
authors: Eduardo E
authors: EE
authors: Valdez-Morales
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors: Nestor N
authors: NN
authors: Jimenez-Vargas
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors: Cintya
authors: C
authors: Lopez-Lopez
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors: Josue
authors: J
authors: Jaramillo-Polanco
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors: Takanobu
authors: T
authors: Okamoto
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.|Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: Yasmin
authors: Y
authors: Nasser
authors: Monash Institute of Pharmaceutical Sciences and Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Australia.|Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia.
authors: Nigel W
authors: NW
authors: Bunnett
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors: Alan E
authors: AE
authors: Lomax
authors: GI Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
authors: Stephen J
authors: SJ
authors: Vanner
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000294:innervation*; D016207:Cytokines / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000502:physiology; D018408:Patch-Clamp Techniques; D015398:Signal Transduction; D013315:Stress, Psychological / Q000503:physiopathology*; D001615:beta-Endorphin / Q000378:metabolism*
chemical_list: D016207:Cytokines; D009270:Naloxone; D001615:beta-Endorphin
keywords: ABDOMINAL PAIN; INFLAMMATORY BOWEL DISEASE; NEUROGASTROENTEROLOGY; PSYCHOLOGICAL STRESS