Abdominal pain and discomfort are common symptoms of Inflammatory bowel disease (IBD) and diagnostic criteria for irritable bowel syndrome (IBS) that significantly impair quality of life. Pain in IBD is thought to be mediated by the activation of pain-sensing nerves (nociceptors) that innervate the bowel by mechanical modalities, such as the distention of visceral organs or by mediators released in response to gut inflammation. Pain management in these conditions is challenging due to the side effects associated with commonly used analgesics, and so a significant unmet clinical need exists for the development of new visceral analgesics. GPR35 is a G- protein-coupled receptor (GPCR) which preferentially signals through the activation of G_αi/o subunits. GPR35 is designated as an “orphan” GPCR due to the ambiguity of its cognate ligand. However, a few synthetic (e.g., zaprinast and cromolyn) and endogenous agonists (e.g., kynurenic acid) have been identified, which have facilitated research into its function (O’Dowdl et al., 1998; Divorty et al., 2015). In recent years, many of these agonists have been shown to be anti-nociceptive in experimental studies of pain signalling. These effects are abolished in GPR35 -/- mice, thereby providing target validation for the analgesic potential of GPR35 agonists (Ohshiro et al., 2008; Cosi et al., 2011; Alexander et al., 2015). In this thesis, I investigated the role of the GPR35 receptor in the regulation of visceral nociception. Our in-silico analysis of previously published transcriptomic data reveals significant co-expression of GPR35 with noxious transducer TRPA1 in the nociceptive neuronal population of colonic DRG neurons. We showed that stimulation of TRPA1 vigorously excites colonic afferents, induces afferent mechanosensitivity and releases neuropeptide Substance-P (SP) from the colonic tissues, which exerts excitatory effects on colonic afferents. Application of the GPR35 receptor agonists cromolyn or zaprinast attenuates TRPA1-induced afferent excitation, relieves mechanosensitivity, and inhibits the release of SP from colonic tissues, thereby restricting the afferent excitation and colonic contractility induced by SP. GPR35 agonists also inhibited the excitatory action of the disease-relevant mediator PGE2. Finally, the involvement of GPR35 as a molecular determinant of cromolyn or zaprinast action was confirmed by repeated experiments in GPR35-/- animal tissues. These findings suggest that GPR35 represents a high-value target for the development of visceral analgesics.