The Role of TRP Channels in Colitis and Inflammatory Bowel Disease: A Systematic Review

Comprising ulcerative colitis (UC) and Crohn's disease (CD), inflammatory bowel disease (IBD) denotes a series of long-standing, relapsing inflammatory disorders of the digestive tract. There is increasing evidence in the literature indicating that IBD pathogenesis is associated with the dysfunction of ion channels, with Transient Receptor Potential (TRP) channels being of particular importance. Through this systematic review, the significance of various TRP channel types in the pathogenesis of colitis and IBD will be appraised. A comprehensive literature search was conducted in PubMed, ScienceDirect, and Google Scholar, encompassing original research articles, using the principles of the PRISMA statement (last search: 15 May 2025). The search terms used were "Transient Receptor Potential Channels", "TRP channels", "TRPV1", "TRPA1", "TRPV4", "TRPV2", "TRPM2", "TRPM3", "TRPM7", "TRPM8", "TRPC3", "colitis", "inflammatory bowel disease", "IBD", "ulcerative colitis", "Crohn Disease". A total of 48 studies met the inclusion criteria. Risk of bias was assessed using SYRCLE's Risk of Bias tool for preclinical studies and the GRADE approach for clinical studies. According to a review of the literature, some TRP channels may exhibit contradictory effects when evaluating pain sensitivity or inflammation, while no conflicting effects have been observed for other TRP channels. Thus, TRPV1 and TRPA1 channels demonstrated opposing effects on pain sensitivity, but TRPV4, TRPM2, TRPM3, and TRPM8 were exclusively linked to elevated pain. Only anti-inflammatory activity was shown for TRPV3, TRPC1, and TRPC6 channels. In contrast, TRPV6, TRPM2, and TRPM3 channels were exclusively associated with a pro-inflammatory role. Concurrently, both pro- and anti-inflammatory effects were manifested for TRPA1, TRPV1, TRPV4, and TRPV5. The literature suggests that these TRP channels exert significant and diverse effects on the pathophysiology of colitis and IBD. Understanding the specific contributions of each TRP channel may pave the way for the development of targeted therapeutic interventions aimed at controlling inflammation and alleviating the symptoms of IBD. This systematic review was funded by the Russian Science Foundation (grant #24-25-00267).