Role of CaMKIIα Leading to Inflammatory and Neuropathic Pain
CaMKII is a major protein kinase that is capable of regulating the activities of many ion channels and receptors. In this study, three animal models were employed to investigate the role of CaMKII in the initiation and maintenance of pain. Inhibition of CaMKII by KN93 dose-dependently reversed inflammatory pain behavior induced by complete Freund’s adjuvant (CFA), neuropathic pain induced by spinal nerve ligation (SNL), as well as opioid-induced hyperalgesia (OIH). To elucidate the specific CaMKII isoform involved, CaMKIIα was targeted by small interfering RNA. Our finding demonstrated that knockdown of spinal CaMKIIα attenuated OIH. Furthermore, morphine failed to induce OIH in CaMKIIαT286A point mutant mice, although wild-type littermate mice developed robust OIH after repeated treatments with morphine. These data implicate an essential role of CaMKIIα as a cellular mechanism leading to inflammatory and neuropathic pain.
Calcium/calmodulin-dependent Protein Kinase II Alpha
Spinal nerve ligation
Complete Freund’s adjuvant