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      Pharmacotherapy for Irritable Bowel Syndrome

      review-article
      Author(s): 1 , * , 2
      Editor(s):
      Publication date (Electronic):
      Journal: Journal of Clinical Medicine
      Publisher: MDPI
      Keywords: diarrhea, constipation, pain, viscera, analgesia

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          Abstract

          Irritable bowel syndrome (IBS) is a disorder of the brain-gut axis; the pathophysiological mechanisms include altered colonic motility, bile acid metabolism, neurohormonal regulation, immune dysfunction, alterations in the epithelial barrier and secretory properties of the gut. This article reviews the mechanisms, efficacy, and safety of current pharmacotherapy, and medications that are in phase III trials for the treatment of IBS. There remains a significant unmet need for effective treatments—particularly for the pain component of IBS—although the introduction of drugs directed at secretion, motility and a non-absorbable antibiotic provide options for the bowel dysfunction in IBS.

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          Guidelines on the irritable bowel syndrome: mechanisms and practical management.

          R Spiller, Q. Aziz, F. Creed … (2007)
          IBS affects 5-11% of the population of most countries. Prevalence peaks in the third and fourth decades, with a female predominance. To provide a guide for the assessment and management of adult patients with irritable bowel syndrome. Members of the Clinical Services Committee of The British Society of Gastroenterology were allocated particular areas to produce review documents. Literature searching included systematic searches using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases and extensive personal reference databases. Patients can usefully be classified by predominant bowel habit. Few investigations are needed except when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse psychological features and somatisation are often present. Ascertaining the patients' concerns and explaining symptoms in simple terms improves outcome. IBS is a heterogeneous condition with a range of treatments, each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; ispaghula improves pain and bowel habit; 5-HT(3) antagonists improve global symptoms, diarrhoea, and pain but may rarely cause unexplained colitis; 5-HT(4) agonists improve global symptoms, constipation, and bloating; selective serotonin reuptake inhibitors improve global symptoms. Better ways of identifying which patients will respond to specific treatments are urgently needed.
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            The role of mast cells in functional GI disorders.

            Mira M Wouters, María Vicario, Javier Cambronero Santos (2016)
            Functional gastrointestinal disorders (FGIDs) are characterized by chronic complaints arising from disorganized brain-gut interactions leading to dysmotility and hypersensitivity. The two most prevalent FGIDs, affecting up to 16-26% of worldwide population, are functional dyspepsia and irritable bowel syndrome. Their etiopathogenic mechanisms remain unclear, however, recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrier function and aberrant neuronal sensitivity. These findings come to challenge the traditional view of FGIDs as pure functional disorders, and relate the origin to a tangible organic substrate. The mucosal inflammatory infiltrate is dominated by mast cells, eosinophils and intraepithelial lymphocytes in the intestine of FGIDs. It is well established that mast cell activation can generate epithelial and neuro-muscular dysfunction and promote visceral hypersensitivity and altered motility patterns in FGIDs, postoperative ileus, food allergy and inflammatory bowel disease. This review will discuss the role of mucosal mast cells in the gastrointestinal tract with a specific focus on recent advances in disease mechanisms and clinical management in irritable bowel syndrome and functional dyspepsia.
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              TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain.

              Boyi Liu, Lu Fan, Shrilatha Balakrishna … (2013)
              Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol- and WS-12-induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                H. Christian Weber: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): J Clin Med
                Journal ID (iso-abbrev): J Clin Med
                Journal ID (publisher-id): jcm
                Title: Journal of Clinical Medicine
                Publisher: MDPI
                ISSN (Electronic): 2077-0383
                Publication date (Electronic): 27 October 2017
                Publication date Collection: November 2017
                Volume: 6
                Issue: 11
                Electronic Location Identifier: 101
                Affiliations
                [1 ]Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) and Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA
                [2 ]Leeds Institute of Biomedical and Clinical Sciences, University of Leeds and Leeds Gastroenterology Institute, Leeds Teaching Hospitals Trust, Leeds LS9 7TF, UK; alexf12399@ 123456yahoo.com
                Author notes
                [* ]Correspondence: camilleri.michael@ 123456mayo.edu ; Tel.: +1-507-266-2305
                Author information
                https://orcid.org/0000-0001-6371-4359
                Article
                Publisher ID: jcm-06-00101
                DOI: 10.3390/jcm6110101
                PMC ID: 5704118
                PubMed ID: 29077050
                SO-VID: 0453adff-818a-489a-aeb3-0c2e36d45d5a
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 02 October 2017
                Date accepted : 24 October 2017
                Categories
                Subject: Review

                Keywords: diarrhea,constipation,pain,viscera,analgesia
                Data availability:
                Keywords: diarrhea, constipation, pain, viscera, analgesia

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