Ca2ϩ /calmodulin-dependent protein kinase II (CaMKII) is a major protein kinase that is capable of regulating the activities of many ion channels and receptors. In the present study, the role of CaMKII in the complete Freund's adjuvant (CFA)-induced inflammatory pain was investigated. Intraplantarly injected CFA was found to induce spinal activity of CaMKII (phosphorylated CaMKII), which was blocked by KN93 [[2-[N-(2-hydroxyethyl) ]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-Nmethylbenzylamine)], a CaMKII inhibitor. Pretreatment with KN93(i.t.) dose-dependently prevented the development of CFAinduced thermal hyperalgesia and mechanical allodynia. Acute treatment with KN93 (i.t.) also dose-dependently reversed CFAinduced thermal hyperalgesia and mechanical allodynia. The action of KN93 started in 30 min and lasted for at least 2 to 4 h.

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