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The identification of new targets to treat postoperative pain is necessary. There is an association of polymorphisms in the Ca<jats:sub>v<\/jats:sub>2.3 gene with postoperative pain and opioid consumption. Our study aimed to identify Ca<jats:sub>v<\/jats:sub>2.3 as a potential target to treat postoperative pain and to reduce opioid\u2010related side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A plantar incision model was established in adult male and female C57BL\/6 mice. Ca<jats:sub>v<\/jats:sub>2.3 expression was detected by qPCR and suppressed by siRNA treatment. The antinociceptive efficacy and safety of a Ca<jats:sub>v<\/jats:sub>2.3 blocker\u2014alone or together with morphine\u2014was also assessed after surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Paw incision in female and male mice caused acute nociception and increased Ca<jats:sub>v<\/jats:sub>2.3 mRNA expression in the spinal cord but not in the incised tissue. Intrathecal treatment with siRNA against Ca<jats:sub>v<\/jats:sub>2.3, but not with a scrambled siRNA, prevented the development of surgery\u2010induced nociception in both male and female mice, with female mice experiencing long\u2010lasting effects. High doses of i.t. SNX\u2010482, a Ca<jats:sub>v<\/jats:sub>2.3 channel blocker, or morphine injected alone, reversed postoperative nociception but also induced side effects. A combination of lower doses of morphine and SNX\u2010482 mediated a long\u2010lasting reversal of postsurgical pain in female and male mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that Ca<jats:sub>v<\/jats:sub>2.3 has a pronociceptive role in the induction of postoperative pain, indicating that it is a potential target for the development of therapeutic approaches for the treatment of postoperative pain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16407","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T05:35:37Z","timestamp":1717047337000},"page":"3594-3609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pronociceptive role of spinal Ca<sub>v<\/sub>2.3 (R\u2010type) calcium channels in a mouse model of postoperative pain"],"prefix":"10.1111","volume":"181","author":[{"given":"Marcella de 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