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      Brain-Gut Interactions in IBS

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          Abstract

          Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with an estimated prevalence of 10–20%. Current understanding of the pathophysiology of IBS is incomplete due to the lack of a clearly identified pathological abnormality and due to the lack of reliable biomarkers. Possible mechanisms believed to contribute to IBS development and IBS like symptoms include physical stressors, such as infection or inflammation, psychological, and environmental factors, like anxiety, depression, and significant negative life events. Some of these mechanisms may involve the brain-gut axis (BGA). In this article we review the current knowledge on the possible involvement of the BGA in IBS and discuss new directions for potential future therapies of IBS.

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          Most cited references 168

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          The need for a new medical model: a challenge for biomedicine.

          The dominant model of disease today is biomedical, and it leaves no room within tis framework for the social, psychological, and behavioral dimensions of illness. A biopsychosocial model is proposed that provides a blueprint for research, a framework for teaching, and a design for action in the real world of health care.
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            Regional dissociations within the hippocampus--memory and anxiety.

            The amnestic effects of hippocampal lesions are well documented, leading to numerous memory-based theories of hippocampal function. It is debatable, however, whether any one of these theories can satisfactorily account for all the consequences of hippocampal damage: Hippocampal lesions also result in behavioural disinhibition and reduced anxiety. A growing number of studies now suggest that these diverse behavioural effects may be associated with different hippocampal subregions. There is evidence for at least two distinct functional domains, although recent neuroanatomical studies suggest this may be an underestimate. Selective lesion studies show that the hippocampus is functionally subdivided along the septotemporal axis into dorsal and ventral regions, each associated with a distinct set of behaviours. Dorsal hippocampus has a preferential role in certain forms of learning and memory, notably spatial learning, but ventral hippocampus may have a preferential role in brain processes associated with anxiety-related behaviours. The latter's role in emotional processing is also distinct from that of the amygdala, which is associated specifically with fear. Gray and McNaughton's theory can in principle incorporate these apparently distinct hippocampal functions, and provides a plausible unitary account for the multiple facets of hippocampal function.
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              Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.

              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. 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. 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). 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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                Author and article information

                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Research Foundation
                1663-9812
                28 April 2012
                05 July 2012
                2012
                : 3
                Affiliations
                1Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz Lodz, Poland
                2Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich Munich, Germany
                Author notes

                Edited by: Angelo A. Izzo, University of Naples Federico II, Italy

                Reviewed by: Cristina Giaroni, University of Insubria, Italy; Peter Christopher Konturek, Teaching Hospital of the University of Jena, Germany

                *Correspondence: Martin A. Storr, Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. e-mail: gidoc@ 123456gmx.com

                This article was submitted to Frontiers in Gastrointestinal Pharmacology, a specialty of Frontiers in Pharmacology.

                Article
                10.3389/fphar.2012.00127
                3389673
                22783191
                Copyright © 2012 Fichna and Storr.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 182, Pages: 12, Words: 12312
                Categories
                Pharmacology
                Review Article

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