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Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome
Open accessAbstract
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.
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In the citing paper
“Notably, approximately 70%–84% of patients with IBS exhibit local mast cell infiltration of mast cells in their intestinal tissues.”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [72]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, the phenomenon of mast cell infiltration surrounding intestinal nerves occurs approximately three times more frequently in IBS patients than in controls, and the number of degranulated mast cells is increased by approximately 1.5-fold (72).”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [72]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Studies on mast cells and cytokines point out that inflammation is present in IBS. 2, 13-20”
From Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota (2008) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“Mucosal mast cell degranulation within the gut can affect host intestinal integrity (Santos et al., 2001) and has been related to visceral pain (Barbara et al., 2004).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Barbara et al., 2004
The cited source says what the claim attributes to it.
In the citing paper
“The severity and frequency of abdominal pain correlates with the presence of activated mast cells in close proximity to nerve endings in the gut mucosa in some studies, 56 but in others mast cell proliferation associates with a reduction, 57 or no change, 58 in visceral sensitivity.”
From British Society of Gastroenterology guidelines on the management of irritable bowel syndrome (2021) · cites this paper as [56]
In the citing paper
“An increase in mucosal immune cells including mast cells, macrophages or monocytes, T-cells, and eosinophils has been reported in both pediatric and adult FGID populations79, 113, 114.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [113]
In the citing paper
“Mast cells were located in closer vicinity to mucosal innervation and correlated with the severity and frequency of abdominal pain in patients with IBS.152”
From Intestinal microbiota in functional bowel disorders: a Rome foundation report (2013) · cites this paper as [152]
In the citing paper
“Evidence supporting this hypothesis includes increased concentrations of inflammatory/immune cells in intestinal tissue from IBS patients, altered levels of pro- and anti-inflammatory cytokines in the GI tract and peripheral blood of patients with IBS (Table 1) (11, 13, 24, 36, 46, 50, 51, 62, 73, 75, 89, 90, 94, 98, 102, 118, 121–124, 168, 174, 185, 187), and IBS-associated polymorphisms in genes”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
In the citing paper
“Other studies have reported elevated levels of histamine and tryptase release in patients with IBS compared with controls (11, 13, 35, 73).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
In the citing paper
“Evidence supporting this hypothesis includes increased concentrations of inflammatory/immune cells in intestinal tissue from IBS patients, altered levels of pro- and anti-inflammatory cytokines in the GI tract and peripheral blood of patients with IBS (Table 1) (11, 13, 24, 36, 46, 50, 51, 62, 73, 75, 89, 90, 94, 98, 102, 118, 121–124, 168, 174, 185, 187), and IBS-associated polymorphisms in genes”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
In the citing paper
“Notably, some studies demonstrated an increase in activated mast cells in biopsies from specific regions of the GI tract (i.e., cecum and terminal ileum) but not from other regions (e.g., ascending colon, descending colon, rectum) (89, 121, 187), whereas other studies have found activated mast cells in the descending colon (11, 13).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
In the citing paper
“Several studies have demonstrated increased concentrations of activated mast cells in patients with IBS compared with controls (11, 13, 24, 46, 89, 94, 121, 187).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
In the citing paper
“Interestingly, the activated mast cells were found to be in close proximity to enteric nerves and correlated with abdominal pain/discomfort (11).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
In the citing paper
“At the peripheral level, the close interaction between the immune system and the ENS in IBS is demonstrated by the increased infiltration of mast cells in the colonic mucosa in close proximity to enteric nerve fibers and by the increased number of sensory nerve fibers surrounding the mast cells (2, 11, 13).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
In the citing paper
“One study that supports this association demonstrated a strong correlation between number of infiltrated colonic mast cells around nerves and the severity and frequency of abdominal pain in patients with IBS (11).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
In the citing paper
“In addition, human and animal studies have shown anatomical changes in the enteric nervous system (ENS) around inflammatory infiltrates in the gut wall (2, 11, 13).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [11]
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Metadata
- Authors
- 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., & Corinaldesi, R.
- Affiliations
- University of Bologna (IT)
- University of California, San Francisco (US)
- McMaster University (CA)
- Corresponding author
- Barbara, Giovanni
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2004-03
- Volume
- 126
- Issue
- 3
- Pages
- 693-702
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W1976068711
- Cited by
- 1,475
- References
- 60
- Citations by year
- 2026: 49 · 2025: 39 · 2024: 49 · 2023: 70 · 2022: 64 · 2021: 74 · 2020: 55 · 2019: 44 · 2018: 74 · 2017: 73 · 2016: 77 · 2015: 71 · 2014: 79 · 2013: 66 · 2012: 84
- FWCI
- 56.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 57840, DK 43207, R01DK057840)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- irritable bowel syndrome, mast cells, abdominal pain, colonic mucosa, enteric nerves, mast cell degranulation, tryptase, histamine release, visceral pain perception, mast cell infiltration
- MeSH terms
- Adult, Aged, Cell Count, Colon, Female, Histamine Release, Humans, Immunohistochemistry, Intestinal Mucosa, Male, Mast Cells, Microscopy, Electron, Middle Aged, Nervous System, Serine Endopeptidases, Blotting, Western, Cell Degranulation, Abdominal Pain, Irritable Bowel Syndrome, Tryptases
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