{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:51:00Z","timestamp":1753883460375,"version":"3.41.2"},"reference-count":26,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p>Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes severe peripheral neuropathy. We previously reported that oxaliplatin (4 mg\/kg, i.p., twice a week) induces mechanical allodynia in the late phase in rats, and that spinal NR2B-containig N-methyl-<jats:sub>D<\/jats:sub>-aspartate (NMDA) receptors are involved in the oxaliplatin-induced mechanical allodynia. In the present study, we investigated the involvement of Ca<jats:sup>2+<\/jats:sup>\/calmodulin dependent protein kinase II (CaMKII), which is a major intracellular protein kinase and is activated by NMDA receptor-mediated Ca<jats:sup>2+<\/jats:sup>influx, in the oxaliplatin-induced mechanical allodynia in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>An increase of CaMKII phosphorylation was found in the spinal cord (L<jats:sub>4-6<\/jats:sub>) of oxaliplatin-treated rats. This increased CaMKII phosphorylation was reversed by intrathecal injection of a selective CaMKII inhibitor KN-93 (50 nmol, i.t.) and a selective NR2B antagonist Ro 25\u20136981 (300 nmol, i.t.). Moreover, acute administration of KN-93 (50 nmol, i.t.) strongly reversed the oxaliplatin-induced mechanical allodynia in von Frey test, while it did not affect the oxaliplatin-induced cold hyperalgesia in acetone test. Similarly, oral administration of trifluoperazine (0.1 and 0.3 mg\/kg, p.o.), which is an antipsychotic drug and inhibits calmodulin, reduced both mechanical allodynia and increased CaMKII phosphorylation. On the other hand, trifluoperazine at the effective dose (0.3 mg\/kg) had no effect on the paw withdrawal threshold in intact rats. In addition, trifluoperazine at the same dose did not affect the motor coordination in rota-rod test in intact and oxaliplatin-treated rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>These results suggest that CaMKII is involved in the oxaliplatin-induced mechanical allodynia, and trifluoperazine may be useful for the treatment of oxaliplatin-induced peripheral neuropathy in clinical setting.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1744-8069-8-26","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T14:14:10Z","timestamp":1334672050000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Inhibition of Ca<sup>2+<\/sup>\/Calmodulin-Dependent Protein Kinase II Reverses Oxaliplatin-Induced Mechanical Allodynia in Rats"],"prefix":"10.1177","volume":"8","author":[{"given":"Masafumi","family":"Shirahama","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soichiro","family":"Ushio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuaki","family":"Egashira","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, 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