Effect of resolvins on sensitisation of TRPV1 and visceral hypersensitivity in IBS

Abstract

ObjectiveResolvins (RvD1, RvD2 and RvE1) are endogenous anti-inflammatory lipid mediators that display potent analgesic properties in somatic pain by modulating transient receptor potential vanilloid 1 (TRPV1) activation. To what extent these molecules could also have a beneficial effect on TRPV1 sensitisation and visceral hypersensitivity (VHS), mechanisms involved in IBS, remains unknown.DesignThe effect of RvD1, RvD2 and RvE1 on TRPV1 activation and sensitisation by histamine or IBS supernatants was assessed on murine dorsal root ganglion (DRG) neurons using live Ca2+ imaging. Based on the results obtained in vitro, we further studied the effect of RvD2 in vivo using a murine model of post-infectious IBS and a rat model of post-inflammatory VHS. Finally, we also tested the effect of RvD2 on submucosal neurons in rectal biopsies of patients with IBS.ResultsRvD1, RvD2 and RvE1 prevented histamine-induced TRPV1 sensitisation in DRG neurons at doses devoid of an analgesic effect. Of note, RvD2 also reversed TRPV1 sensitisation by histamine and IBS supernatant. This effect was blocked by the G protein receptor 18 (GPR18) antagonist O-1918 (3–30 µM) and by pertussis toxin. In addition, RvD2 reduced the capsaicin-induced Ca2+ response of rectal submucosal neurons of patients with IBS. Finally, treatment with RvD2 normalised pain responses to colorectal distention in both preclinical models of VHS.ConclusionsOur data suggest that RvD2 and GPR18 agonists may represent interesting novel compounds to be further evaluated as treatment for IBS.

Differences in dietary habits of people withvswithout irritable bowel syndrome and their association with symptom and psychological status: A pilot study

“…Previous controlled studies have found that patients with functional dyspepsia and IBS were highly sensitive to capsaicin or capsaicin containing foods[ 41 , 42 ]. Capsaicin could act on transient receptor potential vanilloid-1 (TRPV-1) and mediate visceral hypersensitivity[ 43 , 44 ]. A multicenter study involving Korean and Japanese populations found that, regardless of TRPV-1 genotype and Helicobacter pylori infection status, upper gastrointestinal symptoms were more common in patients who ate more spicy foods[ 45 ].…”

Role of microRNAs in Disorders of Gut–Brain Interactions: Clinical Insights and Therapeutic Alternatives

“…A burning sensation and/or pain can be triggered by activation of these channels by capsaicin, acidic pH, thermal stimulus, and/or inflammatory mediators. Studies have shown a positive correlation between the upregulation of TRPV1 expression and abdominal pain in colonic biopsies from patients with IBS-D [67,96]. Further, miR-199a/b has been shown to regulate TRPV1 expression, which has a major role in visceral pain induction in patients with IBS-D [26].…”

Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1

“…To study the effect of GPR18 on TRPV1, neurons were incubated with 10 nM RvD2 and 30 μM O-1918, as described by Perna. 16 The F1/F0 ratio was calculated as the change in the intracellular calcium concentration.…”

“…Some studies have proven that GPR18 is expressed in the central and peripheral nervous systems; 16,18 thus, we decided to study the distribution of GPR18 in the bladder afferent pathway. Immunofluorescence analysis of PGP9.5, a nerve fibre marker, was used to confirm the existence of GPR18 in the bladder afferent pathway in normal bladder specimens.…”

“…15 Likewise, activating GPR18 with RvD2 can inhibit TRPV1 in inflammatory bowel disease. 16 However, the role of GPR18 in IC/BPS is still unclear. In this study, we established an IC/BPS rat model to explore the role of GPR18 in pain and bladder function.…”