title: Intestinal serotonin release, sensory neuron activation, and abdominal pain in irritable bowel syndrome.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Medicine and Center for Applied Biomedical Research, University of Bologna, Bologna, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Cremon
authors.forename: Giovanni
authors.initials: G
authors.lastname: Carini
authors.forename: Bingxian
authors.initials: B
authors.lastname: Wang
authors.forename: Valentina
authors.initials: V
authors.lastname: Vasina
authors.forename: Rosanna F
authors.initials: RF
authors.lastname: Cogliandro
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Stanghellini
authors.forename: David
authors.initials: D
authors.lastname: Grundy
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Ponti
authors.forename: Roberto
authors.initials: R
authors.lastname: Corinaldesi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barbara
mesh_terms: D015746:Abdominal Pain / Q000209:etiology / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002452:Cell Count; D004759:Enterochromaffin Cells / Q000473:pathology*; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000473:pathology*; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D053802:Tryptases / Q000378:metabolism; D017833:Visceral Afferents / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D012701:Serotonin; D006632:Histamine; D053802:Tryptases