Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.
OBJECTIVE
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.
Barbara
Giovanni
G
Departmentof Internal Medicine and Gastroenterology, and CRBA, University of Bologna, Italy. gbarbara@med.unibo.it
Stanghellini
Vincenzo
V
De Giorgio
Roberto
R
Cremon
Cesare
C
Cottrell
Graeme S
GS
Santini
Donatella
D
Pasquinelli
Gianandrea
G
Morselli-Labate
Antonio M
AM
Grady
Eileen F
EF
Bunnett
Nigel W
NW
Collins
Stephen M
SM
Corinaldesi
Roberto
R
D015746:Abdominal Pain / Q000209:etiology*; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002452:Cell Count; D015550:Cell Degranulation; D003106:Colon / Q000294:innervation*; D005260:Female; D006636:Histamine Release; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000294:innervation; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000473:pathology*; D008854:Microscopy, Electron; D008875:Middle Aged; D009420:Nervous System / Q000473:pathology / Q000503:physiopathology; D012697:Serine Endopeptidases / Q000378:metabolism; D053802:Tryptases
D012697:Serine Endopeptidases; D053802:Tryptases