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

Giovanni Barbara, Vincenzo Stanghellini, Roberto De Giorgio, Cesare Cremon, Graeme Cottrell, Donatella Santini, Gianandrea Pasquinelli, Antonio Morselli-Labate, Eileen Grady, Nigel Bunnett, Stephen Collins, Roberto Corinaldesi

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Abstract

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. 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. 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 um 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). Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.
Original languageEnglish
Pages (from-to)693 - 702
Number of pages10
JournalGastroenterology
Volume126
Issue number3
DOIs
Publication statusPublished - 2004

Cite this

Barbara, G., Stanghellini, V., De Giorgio, R., Cremon, C., Cottrell, G., Santini, D., ... Corinaldesi, R. (2004). Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology, 126(3), 693 - 702. https://doi.org/10.1053/j.gastro.2003.11.055
Barbara, Giovanni ; Stanghellini, Vincenzo ; De Giorgio, Roberto ; Cremon, Cesare ; Cottrell, Graeme ; Santini, Donatella ; Pasquinelli, Gianandrea ; Morselli-Labate, Antonio ; Grady, Eileen ; Bunnett, Nigel ; Collins, Stephen ; Corinaldesi, Roberto. / Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. In: Gastroenterology. 2004 ; Vol. 126, No. 3. pp. 693 - 702.
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title = "Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome",
abstract = "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. 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. 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 um 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). Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.",
author = "Giovanni Barbara and Vincenzo Stanghellini and {De Giorgio}, Roberto and Cesare Cremon and Graeme Cottrell and Donatella Santini and Gianandrea Pasquinelli and Antonio Morselli-Labate and Eileen Grady and Nigel Bunnett and Stephen Collins and Roberto Corinaldesi",
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Barbara, G, Stanghellini, V, De Giorgio, R, Cremon, C, Cottrell, G, Santini, D, Pasquinelli, G, Morselli-Labate, A, Grady, E, Bunnett, N, Collins, S & Corinaldesi, R 2004, 'Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome', Gastroenterology, vol. 126, no. 3, pp. 693 - 702. https://doi.org/10.1053/j.gastro.2003.11.055

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. / Barbara, Giovanni; Stanghellini, Vincenzo; De Giorgio, Roberto; Cremon, Cesare; Cottrell, Graeme; Santini, Donatella; Pasquinelli, Gianandrea; Morselli-Labate, Antonio; Grady, Eileen; Bunnett, Nigel; Collins, Stephen; Corinaldesi, Roberto.

In: Gastroenterology, Vol. 126, No. 3, 2004, p. 693 - 702.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome

AU - Barbara, Giovanni

AU - Stanghellini, Vincenzo

AU - De Giorgio, Roberto

AU - Cremon, Cesare

AU - Cottrell, Graeme

AU - Santini, Donatella

AU - Pasquinelli, Gianandrea

AU - Morselli-Labate, Antonio

AU - Grady, Eileen

AU - Bunnett, Nigel

AU - Collins, Stephen

AU - Corinaldesi, Roberto

PY - 2004

Y1 - 2004

N2 - 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. 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. 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 um 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). Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

AB - 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. 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. 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 um 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). Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

U2 - 10.1053/j.gastro.2003.11.055

DO - 10.1053/j.gastro.2003.11.055

M3 - Article

VL - 126

SP - 693

EP - 702

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -