GPR18 as novel target to treat visceral pain

Visceral pain is a hallmark symptom of the irritable bowel syndrome (IBS) for which no efficient treatment is available. It results from sensitisation of TRP (transient receptor potential) channels located on visceral afferent nerves, a phenomenon mediated by histamine released by mast cells. Histamine 1 receptor antagonism blocks TRP sensitisation and improves symptoms in 50% of IBS patients. As TRP channels are also sensitised by other mast cell mediators, therapeutic success will be further improved by intervening with the intracellular mechanism involved in TRP sensitization, an approach that is independent of the initiating trigger. Recently, we showed that resolvin D2 could be an interesting candidate; it prevents and reverses histamine-induced TRPV1 sensitisation via activation of its receptor GPR18, an inhibitory G protein coupled receptor. In this project, we want to further explore the therapeutic potential of GPR18 agonists. These insights are critical for our understanding of IBS and for development of novel treatment modalities.

Keywords:irritable bowel syndrome, visceral pain, TRP channels, resolvins

Disciplines:Gastro-enterology