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Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome

Barbara, G., Stanghellini, V., De Giorgio, R., Cremon, C., Cottrell, G. S., Santini, D., Pasquinelli, G., Morselli-Labate, A. M., Grady, E. F., Bunnett, N. W., Collins, S. M. and Corinaldesi, R. (2004) Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology, 126 (3). pp. 693-702. ISSN 0016-5085

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To link to this item DOI: 10.1053/j.gastro.2003.11.055

Abstract/Summary

BACKGROUND & AIMS: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. METHODS: IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. RESULTS: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). CONCLUSIONS: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
No Reading authors. Back catalogue items
ID Code:30283
Uncontrolled Keywords:Abdominal Pain/*etiology Adult Aged Blotting, Western Cell Count Cell Degranulation Colon/*innervation Female Histamine Release Humans Immunohistochemistry Intestinal Mucosa/innervation Irritable Bowel Syndrome/*complications/*pathology/physiopathology Male Mast Cells/*pathology Microscopy, Electron Middle Aged Nervous System/pathology/physiopathology Serine Endopeptidases/metabolism Tryptases
Additional Information:Barbara, Giovanni Stanghellini, Vincenzo De Giorgio, Roberto Cremon, Cesare Cottrell, Graeme S Santini, Donatella Pasquinelli, Gianandrea Morselli-Labate, Antonio M Grady, Eileen F Bunnett, Nigel W Collins, Stephen M Corinaldesi, Roberto DK43207/DK/NIDDK NIH HHS/ DK57840/DK/NIDDK NIH HHS/ Gastroenterology. 2004 Mar;126(3):693-702.
Publisher:American Gastroenterological Association

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