Zsa Zsa Weerts

TRP channels as therapeutic targets in IBS 75 4 Introduction Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic recurrent abdominal pain and alterations in bowel habit. The pathophysiology of IBS is incompletely understood, which poses obstacles in the search for effective therapeutic approaches. While the defecation pattern can generally be managed adequately with pharmacotherapy, abdominal pain tends to be difficult to treat effectively in IBS patients. In the search for new therapeutic strategies, accumulating interest has been given to peripheral mechanisms of nociception as a key target to develop novel analgesics for IBS-related pain. It is now widely accepted that an altered visceral sensitivity through abnormal endogenous pain processing plays an important role in the pathogenesis. This can result both from peripheral and central sensitization processes. 1 By virtue of peripheral sensitization of nociceptive afferents, increased nociceptive discharge can result in the generation of pain symptoms. 2 The responsiveness of these nociceptive afferents or nociceptors, is determined by the expression of specific channels sensing noxious stimuli. 3 The discovery of sensory transducer molecules, including the transient receptor potential (TRP) channel family has opened a new horizon in understanding peripheral nociceptive processes. TRP channels constitute a family of nonselective cation channels. Several members of this family, of which the Vanilloid 1 capsaicin receptor (TRPV1) has been studied most extensively, have been identified to function as integrators and transducers of nociceptive signals in both somatic and visceral pain. However, as nearly all sensory neurons and several non-neuronal cell types express TRPV1, its role is not limited to nociception. TRP channels indeed appear to have a broad spectrum of functions in the human body, a topic that has been reviewed in detail, elsewhere. 4 This review will focus on current knowledge with regards to the potential role of TRP channels in the pathogenesis of pain symptoms in IBS, with particular emphasis on visceral nociception. Specifically, we will summarise their clinical implications and discuss the future of TRP channel targeted therapy. Methods Evidence to support this review was obtained from an electronic database search via PubMed by two of the authors (AB & ZW) using the search terms “ visceral nociception”, “visceral hypersensitivity”, “irritable bowel syndrome” and “transient receptor potential channels”. The last date of the search was 21 st of July 2017. After screening the abstracts the articles deemed relevant were cross-referenced for additional manuscripts.