Effect of intrathecal injection of KN93, a potent inhibitor of CaMKII, on pain behavior in a mouse model of bone cancer pain

Objective To investigate the role of Ca2+/calmodulin-dependent protein kinase Ⅱ on pain behavior in a mouse model of bone cancer pain. Methods 40 male C3H/HeN mice were divided randomly into 5 groups:sham group (S group, n=8) ,control group (C group, n=8) and KN93 treat group (T1, n=8;T2, n=8;T3, n = 8 ). Group C and T were induced mouse models of bone cancer pain by intra-left-femur inoculations of osteolytic NCTC2472 cells while group S were injected only α-MEM. On the 14 d after inoculations,group S and C received intrathecal injection of 20% DMSO 5 μl . While group T1, T2, T3 received intrathecal injection of KN93 15nmol,30nmol,60nmol which dissolved in 5 μl 20% DMSO respectively. Mice received pain behavior tests including quantification of spontaneous flinches, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) before and at 0.5 h,2 h,4 h,8 h after administration. Results Treatment with KN93(15 nmol) have no effect on bone cancer pain,while treatment with KN93(30 nmol,60 nmol) can dose-dependently reverse quantification of spontaneous flinches, mechanical allodynia and thermal hyperalgesia which were induced by bone cancer pain, At 0. 5h after administration, the quantification of spontaneous flinches of the two groups ( (7.25 + 1.49 ), (4. 12 + 1.36 ) ) were decreased when compared with control group ( 11.62 + 1.92 ),PWMT((1.28 +0.14)g;(1.75 +0.46)g),PWTL((14.64 +2.12) s; (16.85 + 1.61)s)were increased when compared with control group ( (0.47 + 0. 16) g, ( 11.32 + 1.68 ) s) (P ＜ 0.05 ＝. The effect lasts for at least 4 h and disappears at 8 h. Conclusion CaMK Ⅱ may play an important role in the mechanism of bone cancer pain. Intrathecal KN93 injection can effectively attenuated bone cancer pain. Key words: Ca2 +/calmodulin-dependent protein kinase Ⅱ; KN93; Bone cancer pain; Mouse