Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

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Abstract

Context

Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects.

Evidence of Acquisition

In this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia.

Results

Certain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract.

Conclusions

Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target the GI tract and peripheral nerves have better therapeutic profiles by limiting adverse CNS effects.

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Most cited references 81

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Rome IV Diagnostic Questionnaires and Tables for Investigators and Clinicians.

Olafur Palsson, William E Whitehead, Miranda A L van Tilburg … (2016)

The Rome IV Diagnostic Questionnaires were developed to screen for functional gastrointestinal disorders (FGIDs), serve as inclusion criteria in clinical trials, and support epidemiological surveys. Separate questionnaires were developed for adults, children/adolescents, and infants/toddlers. For the adult questionnaire, we first surveyed 1,162 adults without gastrointestinal disorders, and recommended the 90(th) percentile symptom frequency as the threshold for defining what is abnormal. Diagnostic questions were formulated and verified with clinical experts using a recursive process. The diagnostic sensitivity of the questionnaire was tested in 843 patients from 9 gastroenterology clinics, with a focus on clinical diagnoses of irritable bowel syndrome (IBS), functional constipation (FC), and functional dyspepsia (FD). Sensitivity was 62.7% for IBS, 54.7% for FD, and 32.2% for FC. Specificity, assessed in a population sample of 5,931 adults, was 97.1% for IBS, 93.3% for FD, and 93.6% for FC. Excess overlap among IBS, FC, and FD was a major contributor to reduced diagnostic sensitivity, and when overlap of IBS with FC was permitted, sensitivity for FC diagnosis increased to 73.2%. All questions were understandable to at least 90% of individuals, and Rome IV diagnoses were reproducible in ¾ of patients after one month. Validation of the pediatric questionnaires is ongoing.

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Neuropathic pain: principles of diagnosis and treatment.

Ian Gilron, Ralf Baron, Troels Jensen (2015)

Neuropathic pain is caused by disease or injury of the nervous system and includes various chronic conditions that, together, affect up to 8% of the population. A substantial body of neuropathic pain research points to several important contributory mechanisms including aberrant ectopic activity in nociceptive nerves, peripheral and central sensitization, impaired inhibitory modulation, and pathological activation of microglia. Clinical evaluation of neuropathic pain requires a thorough history and physical examination to identify characteristic signs and symptoms. In many cases, other laboratory investigations and clinical neurophysiological testing may help identify the underlying etiology and guide treatment selection. Available treatments essentially provide only symptomatic relief and may include nonpharmacological, pharmacological, and interventional therapies. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and serotonin-norepinephrine reuptake inhibitors) and anticonvulsants (gabapentin and pregabalin). Individualized multidisciplinary patient care is facilitated by careful consideration of pain-related disability (eg, depression and occupational dysfunction) as well as patient education; repeat follow-up and strategic referral to appropriate medical/surgical subspecialties; and physical and psychological therapies. In the near future, continued preclinical and clinical research and development are expected to lead to further advancements in the diagnosis and treatment of neuropathic pain.

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A role for the gut microbiota in IBS.

Francis Collins (2014)

The past decade has witnessed an explosion of knowledge regarding the vast microbial community that resides within our intestine-the gut microbiota. The topic has generated great expectations in terms of gaining a better understanding of disorders ranging from IBD to metabolic disorders and obesity. IBS is a condition for which investigators have long been in search of plausible underlying pathogeneses and it is inevitable that altered composition or function of the gut microbiota will be considered as a potential aetiological factor in at least a subset of patients with IBS. This Review describes the evidence implicating the gut microbiota in not only the expression of the intestinal manifestations of IBS, but also the psychiatric morbidity that coexists in up to 80% of patients with IBS. The evidence described herein ranges from proof-of-concept studies in animals to observational studies and clinical trials in humans. The gut microbiota is subject to influences from a diverse range of factors including diet, antibiotic usage, infection and stress. These factors have previously been implicated in the pathophysiology of IBS and further prompt consideration of a role for the gut microbiota in IBS.

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Author and article information

Journal

Journal ID (nlm-ta): Anesth Pain Med

Journal ID (iso-abbrev): Anesth Pain Med

Journal ID (doi): 10.5812/aapm.

Journal ID (publisher-id): Kowsar

Title: Anesthesiology and Pain Medicine

Publisher: Kowsar

ISSN (Print): 2228-7523

ISSN (Electronic): 2228-7531

Publication date (Electronic): 25 January 2017

Publication date Collection: April 2017

Volume: 7

Issue: 2

Electronic Location Identifier: e42747

Affiliations

[1 ]Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA

Author notes

[* ]Corresponding author: Bin Feng, Ph.D., Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Road, Unit 3247, Storrs, CT 06269-3247, USA. Tel: +1-8604866435, Fax: +1-8604862500, E-mail: fengb@ 123456uconn.edu

Article

DOI: 10.5812/aapm.42747

PMC ID: 5556397

PubMed ID: 28824858

SO-VID: f951824a-9f92-49d8-8c3a-364301be7b46

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

History

Date received : 03 October 2016

Date revision received : 02 December 2016

Date accepted : 24 December 2016

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Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

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Abstract

Context

Evidence of Acquisition

Results

Conclusions

Related collections

Karger: Gastroenterology

Most cited references 81

Rome IV Diagnostic Questionnaires and Tables for Investigators and Clinicians.

Neuropathic pain: principles of diagnosis and treatment.

A role for the gut microbiota in IBS.

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Cited by 26

Most referenced authors 826