{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T21:05:34Z","timestamp":1785618334617,"version":"3.56.0"},"reference-count":69,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The chemotherapy agent oxaliplatin can give rise to oxaliplatin\u2010induced peripheral neuropathy (OIPN). Here, we investigated whether T\u2010type calcium channels (Ca<jats:sub>v<\/jats:sub>3) contribute to OIPN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We chronically treated mice with oxaliplatin and assessed pain responses and changes in expression of Ca<jats:sub>v<\/jats:sub>3.2 calcium channels. We also tested the effects of T\u2010type channel blockers on cold sensitivity in wild\u2010type and Ca<jats:sub>v<\/jats:sub>3.2 null mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Oxaliplatin treatment led to mechanical and cold hypersensitivity in male and female mice. Mechanical hypersensitivity persisted in Ca<jats:sub>v<\/jats:sub>3.2 null mice of both sexes. Intraperitoneal or intrathecal delivery of pan T\u2010type channel inhibitors attenuated mechanical hypersensitivity in wild\u2010type but not Ca<jats:sub>v<\/jats:sub>3.2 null mice. Remarkably cold hypersensitivity occurred in female but not male Ca<jats:sub>v<\/jats:sub>3.2 null mice even without oxaliplatin treatment. Unexpectedly, intrathecal, intraplantar or intraperitoneal delivery of T\u2010type channel inhibitors Z944 or TTA\u2010P2 transiently induced cold hypersensitivity in both male and female wild\u2010type mice. Acute knockdown of specific Ca<jats:sub>v<\/jats:sub>3 isoforms revealed that the depletion of Ca<jats:sub>v<\/jats:sub>3.1 in males and depletion of either Ca<jats:sub>v<\/jats:sub>3.1 or Ca<jats:sub>v<\/jats:sub>3.2 in females triggered cold hypersensitivity. Finally, reducing Ca<jats:sub>v<\/jats:sub>3.2 expression by disrupting the interactions between Ca<jats:sub>v<\/jats:sub>3.2 and the deubiquitinase USP5 with the small organic molecule II\u20102 reversed oxaliplatin\u2010induced mechanical and cold hypersensitivity and importantly did not trigger cold allodynia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Altogether, our data indicate that T\u2010type channels differentially contribute to the regulation of cold and mechanical hypersensitivity, and raise the possibility that T\u2010type channel blockers could promote cold allodynia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17337","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T07:35:16Z","timestamp":1726731316000},"page":"5062-5078","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Contribution of T\u2010type calcium channel isoforms to cold and mechanical sensitivity in na\u00efve and oxaliplatin\u2010treated mice of both sexes"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0620-2984","authenticated-orcid":false,"given":"Flavia T. 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