3 years ago

Review article: transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome

Z. Z. R. M. Weerts, A. B. Beckers, D. Keszthelyi, A. A. M. Masclee, Z. Helyes
Background Abdominal pain in irritable bowel syndrome (IBS) remains challenging to treat effectively. Researchers have attempted to elucidate visceral nociceptive processes in order to guide treatment development. Transient receptor potential (TRP) channels have been implied in the generation (TRPV1, TRPV4, TRPA1) and inhibition (TRPM8) of visceral pain signals. Pathological changes in their functioning have been demonstrated in inflammatory conditions, and appear to be present in IBS as well. Aim To provide a comprehensive review of the current literature on TRP channels involved in visceral nociception. In particular, we emphasise the clinical implications of these nociceptors in the treatment of IBS. Methods Evidence to support this review was obtained from an electronic database search via PubMed using the search terms “visceral nociception,” “visceral hypersensitivity,” “irritable bowel syndrome” and “transient receptor potential channels.” After screening the abstracts the articles deemed relevant were cross-referenced for additional manuscripts. Results Recent studies have resulted in significant advances in our understanding of TRP channel mediated visceral nociception. The diversity of TRP channel sensitization pathways is increasingly recognised. Endogenous TRP agonists, including poly-unsaturated fatty acid metabolites and hydrogen sulphide, have been implied in augmented visceral pain generation in IBS. New potential targets for treatment development have been identified (TRPA1 and TRPV4,) and alternative means of affecting TRP channel signalling (partial antagonists, downstream targeting and RNA-based therapy) are currently being explored. Conclusions The improved understanding of mechanisms involved in visceral nociception provides a solid basis for the development of new treatment strategies for abdominal pain in IBS.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/apt.14294

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