This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron), non-absorbed antibiotic (rifaximin), secretagogues (lubiprostone, linaclotide), μ-opioid receptor (OR) and κ-OR agonist, δ-OR antagonist (eluxadoline), histamine H1 receptor antagonist (ebastine), neurokinin-2 receptor antagonist (ibodutant) and GABAergic agents (gabapentin and pregabalin). Efficacy and safety are discussed based on pivotal trials or published systematic reviews and meta-analysis, expressing ORs or relative risks and their 95% CIs. Potential new approaches may be based on recent insights on mucosal expression of genes, and microRNA and epigenetic markers in human biopsies and in animal models of visceral hypersensitivity.
The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1).
Classes of pharmacological agents for visceral pain
Antidepressants (tricyclic agents, selective serotonin reuptake inhibitors)
5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron)
Non-absorbed antibiotic (rifaximin)
Secretagogues (lubiprostone, linaclotide)
μ-Opioid receptor (OR) and κ-OR agonist and δ-OR antagonist (eluxadoline)
Histamine H1 receptor antagonist (ebastine)
Neurokinin-2 receptor antagonist (ibodutant)
GABAergic agents (gabapentin and pregabalin)
- IRRITABLE BOWEL SYNDROME
- VISCERAL SENSITIVITY
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Contributors Both authors contributed to the writing and revisions of the manuscript.
Funding MC is supported by National Institutes of Health grant R01-DK92179. GB received a research grant from Takeda and is supported by a KU Leuven University Grant (Global Opportunities for Associations GOA 14.011).
Competing interests GB receives research funding from Takeda Pharmaceuticals for IBS pharmacology research unrelated to drugs discussed in this manuscript. He has participated as an invited speaker at a Menarini symposium. On the subject of IBS, MC received research grants from EnteraHealth, Novartis, NGM Pharmaceuticals and NPS Pharma. Also on the subject of IBS, MC performed consulting for Theravance, Takeda, Elobix AB, GlaxoSmithKline, Allergan, Rhythm, Novartis and EA Pharma and participated as an invited speaker at a Menarini symposium with all fees going to his employer, Mayo Clinic.
Provenance and peer review Commissioned; externally peer reviewed.