Gastroenterology

Gastroenterology

Volume 126, Issue 3, March 2004, Pages 693-702
Gastroenterology

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

https://doi.org/10.1053/j.gastro.2003.11.055Get rights and content

Abstract

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 μm 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.

Section snippets

Patients

IBS patients were all seen in the Department of Internal Medicine and Gastroenterology of the University of Bologna and met the Rome II criteria.1 Healthy controls were recruited by public advertisement and included in the study after thorough exclusion of gastrointestinal complaints. None of the study participants were taking nonsteroidal anti-inflammatory drugs or other anti-inflammatory drugs (including mast cell stabilizers, immunosuppressants, and steroids); had undergone major abdominal

Patients

Forty-four consecutive patients with IBS (aged 22–75 years; mean, 40.1 years; 31 females, 13 males) as well as 22 healthy controls (aged 20–71 years; mean, 32.5 years; 12 females, 10 males) participated in the study. All patients complained of abdominal pain/discomfort (severity score: 1.78 ± 1.15; frequency score: 2.20 ± 1.49; mean ± SD); 50% had diarrhea and 50% constipation; furthermore, the most frequently associated symptom was bloating (97.8%).

Mast cell counts

Thirty-four (77.3%) of the 44 IBS patients

Discussion

In this study, we demonstrated that severity and frequency of perceived abdominal painful sensations are correlated with the presence of activated mast cells in proximity of nerve endings in the gut wall. Furthermore, we showed increased histamine and tryptase release by the colonic mucosa of IBS patients. Because these mast cell mediators are known to alter enteric nervous system physiology and induce visceral hypersensitivity,19, 34 their increased release in close proximity to colonic

Acknowledgements

The authors thank Dr. P. Chieco for his help with morphometric studies, Dr. S. Guerrini for her contribution to immunohistochemical studies, Dr. S. Pileri for the generous gift of anti-tryptase antibodies used in the study, and Drs. R. and L. Cogliandro for their contribution to patient selection and management.

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    Supported by the Italian Ministry of University, Research, Science and Technology (to G.B., V.S., R.D.G., and R.C.), by National Institutes of Health grants DK43207 and 57840 (to N.W.B.), by the Canadian Institutes for Health Research (to S.M.C.), and by an educational grant from Janssen (to V.S.).

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