Activation of Human Enteric Neurons by Supernatants of Colonic Biopsy Specimens From Patients With Irritable Bowel Syndrome

Bühner, Sabine; Li, Qin; Vignali, Sheila; Barbara, Giovanni; Giorgio, Roberto De; Stanghellini, Vincenzo; Cremon, Cesare; Zeller, Florian; Langer, Rupert; Daniel, Hannelore; Michel, Klaus; Schemann, Michael

doi:10.1053/j.gastro.2009.07.005

Cited by 302 publications

(358 citation statements)

References 41 publications

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“…The effects and pharmacology of mediators released from the mucosa of IBS patients were also studied on the activity of human submucosal enteric neurons. In this study, authors demonstrated that mediators released from colonic mucosal biopsy of patients with IBS excited neurons of the human submucosal plexus [40]. As demonstrated previously in mice, the excitation was not related to IBS subtypes and may therefore represent a general feature in IBS [40].…”

Section: Implication Of Protease-activated Receptors In Visceral Painsupporting

confidence: 53%

“…In this study, authors demonstrated that mediators released from colonic mucosal biopsy of patients with IBS excited neurons of the human submucosal plexus [40]. As demonstrated previously in mice, the excitation was not related to IBS subtypes and may therefore represent a general feature in IBS [40]. Finally, IBS supernatant-evoked excitation was inhibited by proteases inhibitor and histamine or serotonin receptor antagonists [40].…”

Section: Implication Of Protease-activated Receptors In Visceral Painsupporting

confidence: 51%

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Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Cenac

2013

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Abstract:The protease-activated receptors (PARs) play a pivotal role in inflammatory and nociceptive processes. PARs have raised considerable interest because of their capacity to regulate numerous aspects of viscera physiology and pathophysiology. The present article summarizes research on PARs and proteases as signalling molecules in visceral pain. In particular, experiments in animal models suggest that PAR 2 is important for visceral hypersensitivity. Moreover, endogenous PAR 2 agonists seem to be released by colonic tissue of patients suffering from irritable bowel syndrome, suggesting a role for this receptor in visceral pain perception. Thus, PARs, together with proteases that activate them, represent exciting targets for therapeutic intervention on visceral pain.

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Section: Implication Of Protease-activated Receptors In Visceral Painsupporting

confidence: 53%

Section: Implication Of Protease-activated Receptors In Visceral Painsupporting

confidence: 51%

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Cenac

2013

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“…Th e development and characterization of animal models of visceral hypersensitivity are clearly valuable in understanding how symptoms develop and persist, but as yet no animal model concurrently demonstrates all the symptoms of IBS. Little is known about changes in the peripheral nervous system in IBS patients, mainly due to the diffi culty in accessing visceral neuronal tissue in humans; however, there have been recent promising studies characterizing human GI nerve functions ( 54,119,120 ).…”

Section: Discussionmentioning

confidence: 99%

“…At least two subsets of macrophages have been described, M1 and M2, based on functional diff erences, but much remains to be learned regarding appropriate closer proximity to colonic nerve endings in IBS patients, a fi nding that correlated strongly with severity and frequency of pain ( 55 ). Further, supernatants from mucosal biopsies from IBS patients are more likely to activate intestinal nerves than those from healthy subjects ( 52,54,56,66,68 ). Th is nerve activation is dependent on mast cell-derived mediators, including serine proteases acting on protease-activated receptor-2, histamine acting on its H 1 receptor, and serotonin acting on its 5-HT 3 receptor ( Figure 2 ), and occurs regardless of whether changes in absolute mast cell numbers are observed or not.…”

Section: Antigen-presenting Cellsmentioning

confidence: 99%

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

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

128

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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“…[34][35][36] Moreover, MC mediators, eg, prostaglandins, leukotrienes, and inflammatory cytokines usually are algogenic, and may promote the formation of peripheral sensitization. 37,38 Taken together, MCs activation, along with the MC to nerve signaling, may have an important role in the pathophysiology of visceral hypersensitivity. This concept is further supported by evidence that MC stabilizers such as ketotifen and doxantrazole increased the threshold of pain and improved abdominal discomfort in IBS patients, 35 and decreased the colorectal distension-induced mechanical excitability of colonic C-fibers in IBS-like animals.…”

Section: Mast Cells Modulate Visceral Sensationmentioning

confidence: 99%

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

107

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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Activation of Human Enteric Neurons by Supernatants of Colonic Biopsy Specimens From Patients With Irritable Bowel Syndrome

Cited by 302 publications

References 41 publications

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

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

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

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