title: Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity.
abstract: Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders including functional dyspepsia, irritable bowel syndrome, and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM5, and TRPM8), and modulation of their function by increased activation or sensitization (decreased activation threshold) or altered expression in visceral afferents have been reported in visceral hypersensitivity. TRP channels directly detect or transduce osmotic, mechanical, thermal, and chemosensory stimuli. In addition, pro-inflammatory mediators released in tissue damage or inflammation can activate receptors of the G protein-coupled receptor superfamily leading to TRP channel sensitization and activation, which amplify pain and neurogenic inflammation. In this review, we highlight the present knowledge on the functional roles of neuronal TRP channels in visceral hypersensitivity and discuss the signaling pathways that underlie TRP channel modulation. We propose that a better understanding of TRP channels and their modulators may facilitate the development of more selective and effective therapies to treat visceral hypersensitivity.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium; and.
authors.forename: Dafne
authors.initials: D
authors.lastname: Balemans
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium; and.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Boeckxstaens
authors.affiliation: Laboratory of Ion Channel Research and TRP Research Platform Leuven, Department of Cellular and Molecular Medicine, University of Leuven, Leuven Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Talavera
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium; and mira.wouters@med.kuleuven.be.
authors.forename: Mira M
authors.initials: MM
authors.lastname: Wouters
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000378:metabolism*; D014781:Viscera / Q000294:innervation*; D059265:Visceral Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000700:Analgesics; D018836:Inflammation Mediators; D043562:Receptors, G-Protein-Coupled; D050051:Transient Receptor Potential Channels
keywords: G protein-coupled receptor; TRP channels; hyperalgesia; inflammatory mediators; nociceptor; pain; sensitization; visceral hypersensitivity