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Current treatments are not very effective and new therapeutic approaches are needed. The role of Ca<jats:sub>V<\/jats:sub>3.2 channels, which are important in other chronic pain contexts, was investigated in a murine model of colonic hypersensitivity (CHS) associated with low\u2010grade inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Low doses of dextran sulfate sodium (DSS; 0.5%) were chronically administered to C57BL\/6j mice in drinking water. Their inflammatory state was assessed by systemic and local measures of IL\u20106, myeloperoxidase, and lipocalin\u20102 using <jats:sc>elisa<\/jats:sc>. Colonic sensitivity was evaluated by the visceromotor responses to colorectal distension. Functional involvement of Ca<jats:sub>V<\/jats:sub>3.2 channels was assessed with different pharmacological (TTA\u2010A2, ABT\u2010639, and ethosuximide) and genetic tools.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>DSS induced low\u2010grade inflammation associated with CHS in mice. Genetic or pharmacological inhibition of Ca<jats:sub>V<\/jats:sub>3.2 channels reduced CHS. Cav3.2 channel deletion in primary nociceptive neurons in dorsal root ganglia (Ca<jats:sub>V<\/jats:sub>3.2<jats:sup>Nav1.8<\/jats:sup> KO mice) suppressed CHS. Spinal, but not systemic, administration of ABT\u2010639, a peripherally acting T\u2010type channel blocker, reduced CHS. ABT\u2010639 given intrathecally to Ca<jats:sub>V<\/jats:sub>3.2<jats:sup>Nav1.8<\/jats:sup> KO mice had no effect, demonstrating involvement of Ca<jats:sub>V<\/jats:sub>3.2 channels located presynaptically in afferent fibre terminals. Finally, ethosuximide, which is a T\u2010type channel blocker used clinically, reduced CHS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These results suggest that ethosuximide represents a promising drug reposition strategy and that inhibition of Ca<jats:sub>V<\/jats:sub>3.2 channels is an attractive therapeutic approach for relieving CHS in IBS or IBD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14608","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T09:55:11Z","timestamp":1549274111000},"page":"950-963","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Inhibition of Ca<sub>v<\/sub>3.2 calcium channels: A new target for colonic hypersensitivity associated with low\u2010grade inflammation"],"prefix":"10.1111","volume":"176","author":[{"given":"Elodie","family":"Picard","sequence":"first","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne INSERM, CHU, NEURO\u2010DOL Basics &amp; 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