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Neurogastroenterol Motil. 2016 Nov;28(11):1632-1640. doi: 10.1111/nmo.12860. Epub 2016 May 15.

Colonic overexpression of the T-type calcium channel Cav 3.2 in a mouse model of visceral hypersensitivity and in irritable bowel syndrome patients.

Author information

1
Centre Hospitalier Universitaire Estaing, Department of Digestive Diseases, CHU Clermont-Ferrand, Clermont-Ferrand, France. jscanzi@chu-clermontferrand.fr.
2
Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France. jscanzi@chu-clermontferrand.fr.
3
Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
4
Centre Hospitalier Universitaire G. Montpied, Biostatistics Unit (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, France.
5
Centre Hospitalier Universitaire Estaing, Department of Digestive Diseases, CHU Clermont-Ferrand, Clermont-Ferrand, France.
6
Centre Hospitalier Universitaire Estaing, Department of Histopathology, CHU Estaing Clermont-Ferrand, Clermont-Ferrand, France.

Abstract

BACKGROUND:

Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav 3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients.

METHODS:

This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav 3.2-KO mice. Colonic sensitivity and Cav 3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav 3.2 expression.

KEY RESULTS:

Wild-type, but not Cav 3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav 3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav 3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers.

CONCLUSIONS & INFERENCES:

This translational study supports the involvement of the calcium channels Cav 3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.

KEYWORDS:

calcium channel; colonic hypersensitivity; irritable bowel syndrome; visceral pain

PMID:
27196538
DOI:
10.1111/nmo.12860
[Indexed for MEDLINE]

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