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 (0.370.16% vs. 0.560.26%; 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-HT 3 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.

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

CREMON, CESARE;CARINI, GIOVANNI;VASINA, VALENTINA;COGLIANDRO, ROSANNA FRANCESCA;DE GIORGIO, ROBERTO;STANGHELLINI, VINCENZO;TONINI, MARCELLO;DE PONTI, FABRIZIO;CORINALDESI, ROBERTO;BARBARA, GIOVANNI
2011

Abstract

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 (0.370.16% vs. 0.560.26%; 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-HT 3 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.
2011
Cremon C; Carini G; Wang B; Vasina V; Cogliandro RF; De Giorgio R; Stanghellini V; Grundy D; Tonini M; De Ponti F; Corinaldesi R; Barbara G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/112129
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