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.
Cremon C, Carini G, Wang B, Vasina V, Cogliandro RF, De Giorgio R, et al. (2011). Intestinal serotonin release, sensory neuron activation, and abdominal pain in irritable bowel syndrome. THE AMERICAN JOURNAL OF GASTROENTEROLOGY, 106, 1290-1298 [10.1038/ajg.2011.86].
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
