Participation of spinal CaMKII-NR2B signal pathway in the development of bone cancer pain in mice / 中华行为医学与脑科学杂志

ABSTRACT

ObjectiveTo investigate the effect of KN93,a CaMKII inhibitor,on the spinal NR2B expression in the bone cancer pain mouse and its underlying mechanism.MethodsThirty-six male C3IL/IIeJ mice were randomly divided into 3 groupssham group( S,n =8 ),bone cancer pain group( BP,n =8 ) and KN93 group ( K,n=20).The mouse model of bone cancer pain was established by intra-femur inoculation of osteolytie NCTC 2472 cells in BP and K groups.At 14d post operation,mice in K group received intrathecal injection of 60nmol KN93/5μl in 20％ DMSO and mice in BP group and S group received 20％ DMSD 5μl respectively.Eight mice were selected randomly from each group at (1)d before inoculation,at 1 h before administration and at 1,2,4,24h after administration( T0-5 ) to be measured the paw withdrawal threshold(PWT) stimulated by von Frey filaments.Another 3 mice were sacrificed at the corresponding time point and the spinal cord L3 -5 were obtained for determination of NR2B expression by western blot.ResultsPWT was significantly decreased in group BP( (0.50 ± 0.11 ) g) and K( (0.52 ±0.10)g),except for group K at T3(P＞0.05),and NR2B cxpression up-regulated at T2-5 in BP( 1.78± 0.34),K groups ( ( 1.11 ± 0.14),(0.73 ± 0.03 ),( 1.11 ± 0.15 ),( 1.89 ± 0.32 ) ) compared with S group ( ( 1.78 ± 0.31 ) g,(0.33 ± 0.04),P ＜ 0.05 ).Compared with group BP,PWT was increased and NR2B expression down-regulated at T2-4 in group K.In contrast to T1,PWT at T2-4 upgraded in group K(P＜0.05 ),but no significant difference was observed in other groups (P＞ 0.05 ).ConclusionIntrathecal injection of KN93 can attenuate bone cancer pain in mice through inhibiting NR2B with a time-dependent manner and spinal CaMKII-NR2B pathway may participate in the development of bone cancer pain.