Ca2+/calmodulin-protein kinase IIα in the trigeminal subnucleus caudalis contributes to neuropathic pain following inferior alveolar nerve transection

Calcium-calmodulin protein kinase IIα (CaMKIIα) is mainly found in brain cells, and the mRNA concentrates highly in the postsynaptic density. CaMKIIα is an effector of calcium and calmodulin mediated functions, and the phosphorylated CaMKIIα (pCaMKIIα) activates glutamate receptors, such as the AMPA receptor, and enhances its function. In the present study, we examined whether CaMKIIα in trigeminal brainstem neurons contributed to the neuropathic pain induced by inferior alveolar nerve (IAN) transection. Using immunohistochemistry and in situ hybridization, we found that the expression of CaMKIIα and pCaMKIIα increased in the trigeminal subnucleus caudalis (Vc) after IAN transection. The significant increase in the protein of CaMKIIα peaked at 30 min after IAN transection, and the mRNA of CaMKIIα increased from 2 to 14 days. Double immunofluorescent staining for CaMKIIα and MAP2, a marker of dendrite, revealed a significant increase in the overlapping area at 30 min after injury. This suggests that CaMKIIα protein is synthesized from the local mRNA pool in the dendrite 30 min after IAN transection and may quickly transmit information after nerve injury. In the behavioral test in which the escape threshold from mechanical stimulation to the lateral face was measured, intrathecal administration of KN-93, a CaMKII inhibitor, for 7 days significantly inhibited mechano-allodynia induced by IAN transection, as compared with administration of a control peptide. These data suggest that CaMKIIα in the trigeminal subnucleus caudalis may be involved in neuropathic pain caused by IAN transection.