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

A. B. Beckers, Z. Z.R.M. Weerts, Z. Helyes, A. A.M. Masclee, D. Keszthelyi

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)938-952
Number of pages15
JournalAlimentary Pharmacology and Therapeutics
Volume46
Issue number10
DOIs
Publication statusPublished - Nov 1 2017

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Transient Receptor Potential Channels
Irritable Bowel Syndrome
Nociception
Visceral Pain
Abdominal Pain
Therapeutics
Hydrogen Sulfide
Nociceptors
Manuscripts
Unsaturated Fatty Acids
PubMed
Hypersensitivity
Research Personnel
Databases
RNA

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Review article : transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome. / Beckers, A. B.; Weerts, Z. Z.R.M.; Helyes, Z.; Masclee, A. A.M.; Keszthelyi, D.

In: Alimentary Pharmacology and Therapeutics, Vol. 46, No. 10, 01.11.2017, p. 938-952.

Research output: Contribution to journalReview article

Beckers, A. B. ; Weerts, Z. Z.R.M. ; Helyes, Z. ; Masclee, A. A.M. ; Keszthelyi, D. / Review article : transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome. In: Alimentary Pharmacology and Therapeutics. 2017 ; Vol. 46, No. 10. pp. 938-952.
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abstract = "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.",
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