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5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D.

ABSTRACT: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-oxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-oxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-oxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca2+ imaging of dorsal root ganglion (DRG) neurons. We showed that 5-oxoETE selectively stimulated nonpeptidergic, isolectin B4 (IB4)-positive DRG neurons through a phospholipase C (PLC)- and pertussis toxin-dependent mechanism, suggesting that the effect was mediated by a G protein-coupled receptor (GPCR). The MAS-related GPCR D (Mrgprd) was found in mouse colonic DRG afferents and was identified as being implicated in the noxious effects of 5-oxoETE. Together, these data suggest that 5-oxoETE, a potential biomarker of IBS-C, induces somatic and visceral hyperalgesia without inflammation in an Mrgprd-dependent manner. Thus, 5-oxoETE may play a pivotal role in the abdominal pain associated with IBS-C.

SUBMITTER: Bautzova T

PROVIDER: S-EPMC6411128 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D.

Bautzova Tereza T Hockley James R F JRF Perez-Berezo Teresa T Pujo Julien J Tranter Michael M MM Desormeaux Cleo C Barbaro Maria Raffaella MR Basso Lilian L Le Faouder Pauline P Rolland Corinne C Malapert Pascale P Moqrich Aziz A Eutamene Helene H Denadai-Souza Alexandre A Vergnolle Nathalie N Smith Ewan St John ESJ Hughes David I DI Barbara Giovanni G Dietrich Gilles G Bulmer David C DC Cenac Nicolas N

Science signaling 20181218 561

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectromet ...[more]

PMID: 30563864

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Project description:In this study, we aim to evaluate the efficacy and safety of acupoint catgut embedding for the treatment of diarrhea-predominant irritable bowel syndrome and constipation-predominant irritable bowel syndrome. We searched seven online databases to collect studies published up to Feb 29th, 2020. Study quality of each included article was evaluated by the Cochrane Collaboration Risk of Bias Tool. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan 5.3 software. Among the included trials, acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapies, or plus oral traditional Chinese medicine were the main therapies in the experimental groups. Interventions in control groups mainly include oral western medicine alone, other acupoint-based therapies alone, or other acupoint-based therapies alone. Primary outcomes in this study include recovery rate, accumulative marked effective rate, accumulative effective rate, and recurrence rate. Finally, 30 trials involving 1889 participants were included. The results of systematic reviews and meta-analyses show that acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapy or plus oral traditional Chinese medicine was significantly better compared with using oral western medicine alone in terms of efficacy for IBS-C and IBS-D. In addition, acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapy or plus oral traditional Chinese medicine could improve the effective rate and decrease the recurrence rate for IBS-D compared with using oral western medicine, other acupoint-based therapies, or oral traditional Chinese medicine alone. Adverse events of acupoint catgut embedding include local induration, redness, swelling, and itchiness, but they were all mild and disappeared swiftly with ordinary local interventions. There is an urgent need for RCTs of high quality and large sample size and with longer treatment duration and follow-up periods of acupoint catgut embedding for IBS.

Project description:Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic or recurrent abdominal pain in association with defecation or a change in bowel habits. A predominant disorder of bowel habits, IBS is classified into three main subtypes: constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D) and IBS alternating between constipation and diarrhea (IBS-M). Linaclotide is a first-in-class, oral, once-daily guanylate cyclase-C receptor agonist (GC-CA) that is licensed for the symptomatic treatment of moderate-to-severe IBS-C in adults. This review aims to facilitate and optimize clinical practices, establishing common guidelines to monitor patients with IBS-C that are treated with linaclotide.A group of experts in functional digestive disorders was convened to review the efficacy and safety of linaclotide and to develop an updated consensus report for the treatment of patients with IBS-C. A search was performed for English, French and Spanish language articles in PubMed. On the basis of the articles identified, an initial document was drafted addressing different issues frequently raised by general practitioners and GI specialists that are related to the prescription, efficacy and safety of linaclotide. This document was then reviewed and modified by the expert panel until a final text was agreed upon and validated.Based on the evidence, the panel addressed the following recommendations: (1) Linaclotide is indicated for the treatment of moderate to severe IBS-C in adults; (2) it is recommended that patients take linaclotide continuously and not sporadically; (3) patients should be warned about the risk of diarrhea and given choices concerning how to deal with this possible side effect; (4) the absence of tachyphylaxis or potential risks implies that linaclotide treatment can be maintained for long periods of time.This document seeks to lay down a set of recommendations and to identify key issues that may be useful for the clinical management of IBS-C patients treated with linaclotide.

Dataset Information

5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D.

Publications

5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D.

Similar Datasets

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