Intestinal serotonin release, sensory neuron activation, and abdominal pain in irritable bowel syndrome

Am J Gastroenterol. 2011 Jul;106(7):1290-8. doi: 10.1038/ajg.2011.86. Epub 2011 Mar 22.


Objectives: Serotonin (5-hydroxytryptamine, 5-HT) metabolism may be altered in gut disorders, including in the irritable bowel syndrome (IBS). We assessed in patients with IBS vs. healthy controls (HCs) the number of colonic 5-HT-positive cells; the amount of mucosal 5-HT release; their correlation with mast cell counts and mediator release, as well as IBS symptoms; and the effects of mucosal 5-HT on electrophysiological responses in vitro.

Methods: We enrolled 25 Rome II IBS patients and 12 HCs. IBS symptom severity and frequency were graded 0-4. 5-HT-positive enterochromaffin cells and tryptase-positive mast cells were assessed with quantitative immunohistochemistry on colonic biopsies. Mucosal 5-HT and mast cell mediators were assessed by high-performance liquid chromatography or immunoenzymatic assay, respectively. The impact of mucosal 5-HT on electrophysiological activity of rat mesenteric afferent nerves was evaluated in vitro.

Results: Compared with HCs, patients with IBS showed a significant increase in 5-HT-positive cell counts (0.37 ± 0.16% vs. 0.56 ± 0.26%; P=0.039), which was significantly greater in patients with diarrhea-predominant IBS vs. constipation-predominant IBS (P=0.035). Compared with HCs, 5-HT release in patients with IBS was 10-fold significantly increased (P < 0.001), irrespective of bowel habit, and was correlated with mast cell counts. A significant correlation was found between the mucosal 5-HT release and the severity of abdominal pain (r(s)=0.582, P=0.047). The area under the curve, but not peak sensory afferent discharge evoked by IBS samples in rat jejunum, was significantly inhibited by the 5-HT₃ receptor antagonist granisetron (P<0.005).

Conclusions: In patients with IBS, 5-HT spontaneous release was significantly increased irrespective of bowel habit and correlated with mast cell counts and the severity of abdominal pain. Our results suggest that increased 5-HT release contributes to development of abdominal pain in IBS, probably through mucosal immune activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / etiology
  • Abdominal Pain / metabolism*
  • Adult
  • Animals
  • Cell Count
  • Enterochromaffin Cells / pathology*
  • Female
  • Histamine / metabolism
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology*
  • Irritable Bowel Syndrome / complications
  • Irritable Bowel Syndrome / metabolism*
  • Irritable Bowel Syndrome / pathology
  • Jejunum / drug effects
  • Jejunum / physiology
  • Male
  • Mast Cells / pathology*
  • Middle Aged
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Serotonin / pharmacology
  • Tryptases / metabolism
  • Visceral Afferents / drug effects
  • Visceral Afferents / physiology
  • Young Adult


  • Serotonin
  • Histamine
  • Tryptases