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Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity.
Am J Physiol Gastrointest Liver Physiol. 2017 Jun 01; 312(6):G635-G648.AJ

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+Show Affiliations

Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium; and.Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium; and.Laboratory of Ion Channel Research and TRP Research Platform Leuven, Department of Cellular and Molecular Medicine, University of Leuven, Leuven Belgium.Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium; and mira.wouters@med.kuleuven.be.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28385695

Citation

Balemans, Dafne, et al. "Transient Receptor Potential Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades Underlying Visceral Hypersensitivity." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 312, no. 6, 2017, pp. G635-G648.
Balemans D, Boeckxstaens GE, Talavera K, et al. Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol. 2017;312(6):G635-G648.
Balemans, D., Boeckxstaens, G. E., Talavera, K., & Wouters, M. M. (2017). Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity. American Journal of Physiology. Gastrointestinal and Liver Physiology, 312(6), G635-G648. https://doi.org/10.1152/ajpgi.00401.2016
Balemans D, et al. Transient Receptor Potential Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades Underlying Visceral Hypersensitivity. Am J Physiol Gastrointest Liver Physiol. 2017 Jun 1;312(6):G635-G648. PubMed PMID: 28385695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity. AU - Balemans,Dafne, AU - Boeckxstaens,Guy E, AU - Talavera,Karel, AU - Wouters,Mira M, Y1 - 2017/04/06/ PY - 2016/11/15/received PY - 2017/03/21/revised PY - 2017/04/01/accepted PY - 2017/4/8/pubmed PY - 2017/8/12/medline PY - 2017/4/8/entrez KW - G protein-coupled receptor KW - TRP channels KW - hyperalgesia KW - inflammatory mediators KW - nociceptor KW - pain KW - sensitization KW - visceral hypersensitivity SP - G635 EP - G648 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 312 IS - 6 N2 - 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. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/28385695/Transient_receptor_potential_ion_channel_function_in_sensory_transduction_and_cellular_signaling_cascades_underlying_visceral_hypersensitivity_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00401.2016?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -