Analgesic effect of intrathecal KN93 on neuropathic pain in mice

Objective To explore the role of Ca2+/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ) in the mechanism of neuropathic pain.Methods Thirty-two adult male ICR mice were randomly divided into 4 groups with 8 mice each.After L5/6 spinal nerve ligation(SNL) neuropathic pain model was established,the mice in group A were given nothing,those in group B were intrathecally given KN92 45nmol,those in group C were intrathecally given KN93 45nmol,and those in group D were treated as sharm operated rats.Mechanical and thermal pain thresholds were determined by paw withdrawal latency/threshold to von Frey hair or radiant heat stimulation before SNL and on the 2nd,3rd,4th,and 5th day after SNL.KN93 or KN92 were administered 30min before last test of pain threshold.After last test of pain threshold,the mice were sacrificed and lumbar spinal tissues were sampled for analysis of the expression of pCaMKⅡ by Western blot.Results Mechanical and thermal pain thresholds were dramatically decreased and the expression of pCaMKⅡ was obviously increased by SNL(P0.05),and these changes were reversed by KN93(P0.05),but not by KN92.Conclusion CaMKⅡ may play a role in the development of chronic neuropathic pain induced by SNL.Therapeutics targeting CaMKⅡ signal pathway may be a potent candidate for future therapy of chronic neuropathic pain.