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

Barbara, Giovanni; Stanghellini, Vincenzo; Giorgio, Roberto De; Cremon, Cesare; Cottrell, Graeme S.; Santini, Donatella; Pasquinelli, Gianandrea; Morselli-Labate, Antonio Maria; Grady, Eileen F.; Bunnett, Nigel W.; Collins, Stephen M.; Corinaldesi, Roberto

doi:10.1053/j.gastro.2003.11.055

Cited by 1,236 publications

(1,312 citation statements)

References 54 publications

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“…We speculate if there is a different aetiology in idiopathic IBS compared with IBS in CD and UC. Further, the heterogenous histopathologic abnormalities found in different studies regarding functional gastrointestinal disorders suggest that the primary aetiology may differ between IBS patients (3,24,25,26). The discrepancy between autonomic nervous tests and functional bowel symptoms implies that histopathological examination is necessary to diagnose enteric neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Enteric ganglioneuritis and abnormal interstitial cells of Cajal

Ohlsson

Veress

Lindgren

et al. 2007

Inflammatory Bowel Diseases

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Section: Discussionmentioning

confidence: 99%

Enteric ganglioneuritis and abnormal interstitial cells of Cajal

Ohlsson

Veress

Lindgren

et al. 2007

Inflammatory Bowel Diseases

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“…However, reports of variation in the absolute number of mast cells in the intestine are confl icting, as a similar number of studies indicate mast cell numbers are increased or unchanged in IBS patients ( Table 2 ) ( 44,48 -67 ). In those studies that observed increased mast cell numbers, correlations with symptoms are also mixed ( Table 1 ) ( 37,41,50,52,53,55,59,63 ). Despite this contention, the absolute number of mast cells may not be the defi ning characteristic of their involvement in IBS.…”

Section: Mast Cellsmentioning

confidence: 99%

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

132

117

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Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterized by pain or discomfort from the lower abdominal region, which is associated with altered bowel habit. Despite its prevalence, there is currently a lack of effective treatment options for patients. IBS has long been considered as a neurological condition resulting from alterations in the brain gut axis, but immunological alterations are increasingly reported in IBS patients, consistent with the hypothesis that there is a chronic, but low-grade, immune activation. Mediators released by immune cells act to either dampen or amplify the activity of GI nerves. Release of a number of these mediators correlates with symptoms of IBS, highlighting the importance of interactions between the immune and the nervous systems. Investigation of the role of microbiota in these interactions is in its early stages, but may provide many answers regarding the mechanisms underlying activation of the immune system in IBS. Identifying what the key changes in the GI immune system are in IBS and how these changes modulate viscerosensory nervous function is essential for the development of novel therapies for the underlying disorder.

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“…Th ere are many indicators to suggest that mast cell activation rather than mast cell numbers should be studied ( 11 ). Mast cells are located close to blood vessels and enteric nerve endings ( 5,12 ) and their mediators through these pathways can activate control systems of colonic motility. Th is does not need to involve degranulation.…”

Section: Guarantorsmentioning

confidence: 99%

“…Th erefore, immune cell infi ltration assessed in mucosal biopsies may provide critical information on the mechanisms of symptom generation. Both intestinal ( 4 ) and colonic ( 5,6 ) biopsies have been investigated. Mast cells have received particular attention because its secretory products, such as histamine, prostaglandins, and proteinases, are capable of sensorimotor dysfunction.…”

mentioning

confidence: 99%

Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

Theoharides¹,

Asadi²,

Chen³

et al. 2012

American Journal of Gastroenterology

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Irritable bowel syndrome (IBS) is the most common condition seen by gastroenterologists. It presents with alternating symptoms of bowel dysfunction that often worsens with stress. The cause of these symptoms eludes investigators and many attempts have been made to discover an underlying pathology. This is a daunting task since symptoms come and go, and change characteristics. Furthermore, the pathology of IBS is unlikely to be identical in all patients. In addition, all symptoms and all features studied thus far have a strong overlap with healthy volunteers. Elsewhere in this issue, Braak et al. report a well-designed clinical investigation in patients with IBS and come to the conclusion that IBS is not characterized by mast cell or other immune cell proliferation, but by immune dysregulation in the colon. Is this the fi nal answer? Am J Gastroenterol 2012; 107:727 -729; doi: 10.1038/ajg.2012 Irritable bowel syndrome (IBS) is a common functional disorder in the West ( 1 ) and in Asia ( 2 ), which is characterized clinically as abdominal discomfort or pain with alternating constipation and diarrhea. Mechanistic pathways to symptom generation are unclear, although dysfunction of brain-gut communication, gut motility, visceral perception, neuroimmune responses, infl ammation, and mucosal integrity, as well as the psychosocial status might be involved ( 3 ). Th e mucosa contains endings of the enteric sensory nerves; these aff erent nerves can modify motility and pain perception. Th erefore, immune cell infi ltration assessed in mucosal biopsies may provide critical information on the mechanisms of symptom generation. Both intestinal ( 4 ) and colonic ( 5,6 ) biopsies have been investigated. Mast cells have received particular attention because its secretory products, such as histamine, prostaglandins, and proteinases, are capable of sensorimotor dysfunction. IBS appears to worsen with stress and the important information might be obtained from relationships between stress, corticotropin-releasing hormone (CRH) and symptoms ( 7 ). CRH signaling pathways have been shown to have an important role in stress-related alterations of gut function related to intestinal symptoms ( 7 ). Braak et al. ( 8 ) have attempted to clarify IBS pathophysiology using these strategies.Mast cells are well known to modulate gastrointestinal pathophysiology and are considered to be involved in IBS ( 9 ). Increased numbers of mast cells have been reported in the terminal ileum in patients with IBS, although there was lack of correlation with diarrhea-predominant IBS symptoms ( 4 ). Braak et al. ( 8 ) conclude that the number of mast cells, macrophages (CD68), T cells (CD3 and CD8), and λ FLC-positive mast cells is decreased in IBS patients compared with healthy volunteers. As a general statement, this needs clarifi cation. Th ey note the decrease in the descending colon, but no change was seen in the ascending colon and immune cell numbers in the small intestine were not measured. Furthermore, mast cells in the gut musculature ( ...

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

Cited by 1,236 publications

References 54 publications

Enteric ganglioneuritis and abnormal interstitial cells of Cajal

Enteric ganglioneuritis and abnormal interstitial cells of Cajal

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Editorial: Irritable Bowel Syndrome and the Elusive Mast Cells

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