Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons

Neurogastroenterol Motil. 2010 Jun;22(6):654-e202. doi: 10.1111/j.1365-2982.2010.01477.x. Epub 2010 Mar 4.


Background: The pathogenesis of inflammatory bowel disease is unknown; however, the disorder is aggravated by psychological stress and is itself psychologically stressful. Chronic intestinal inflammation, moreover, has been reported to activate forebrain neurons. We tested the hypotheses that the chronically inflamed bowel signals to the brain through the vagi and that administration of a combination of secretin (S) and oxytocin (OT) inhibits this signaling.

Methods: Three daily enemas containing 2,4,6-trinitrobenzene sulfonic acid (TNBS), which were given to rats produced chronic colitis and ongoing activation of Fos in brain neurons.

Key results: Fos was induced in neurons in the paraventricular nucleus of the hypothalamus, basolateral amygdala, central amygdala, and piriform cortex. Subdiaphragmatic vagotomy failed to inhibit this activation of Fos, suggesting that colitis activates forebrain neurons independently of the vagi. When administered intravenously, but not when given intracerebroventricularly, in doses that were individually ineffective, combined S/OT prevented colitis-associated activation of central neurons. Strikingly, S/OT decreased inflammatory infiltrates into the colon and colonic expression of tumor necrosis factor-alpha and interferon-gamma.

Conclusions & inferences: These observations suggest that chronic colonic inflammation is ameliorated by the systemic administration of S/OT, which probably explains the parallel ability of systemic S/OT to inhibit the colitis-associated activation of forebrain neurons. It is possible that S and OT, which are endogenous to the colon, might normally combine to restrict the severity of colonic inflammatory responses and that advantage might be taken of this system to develop novel means of treating inflammation-associated intestinal disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Animals
  • Cerebral Cortex / drug effects
  • Chronic Disease
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / pathology
  • Genes, fos / drug effects
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Interferon-gamma / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Neurons / drug effects*
  • Oxytocin / administration & dosage
  • Oxytocin / pharmacology*
  • Oxytocin / therapeutic use
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Prosencephalon / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Secretin / administration & dosage
  • Secretin / pharmacology*
  • Secretin / therapeutic use
  • Signal Transduction / drug effects
  • Trinitrobenzenesulfonic Acid
  • Tumor Necrosis Factor-alpha / metabolism
  • Vagotomy


  • Tumor Necrosis Factor-alpha
  • Secretin
  • Oxytocin
  • Interferon-gamma
  • Trinitrobenzenesulfonic Acid