DIFFERENTIAL EXPRESSION OF PHOSPHORYLATED Ca2+/CALMODULIN-DEPENDENT PROTEIN KINASE II AND PHOSPHORYLATED EXTRACELLULAR SIGNAL-REGULATED PROTEIN IN THE MOUSE HIPPOCAMPUS INDUCED BY VARIOUS NOCICEPTIVE STIMULI

In the present study, we characterized differential expressions of phosphorylated Ca2+/calmodulin-dependent protein kinase II alpha (pCaMKII alpha) and phosphorylated extracellular signal-regulated protein (pERK) in the mouse hippocampus induced by various nociceptive stimuli. In an immunoblot study, s.c. injection of formalin and intrathecal (i.t.) injections of glutamate, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) significantly increased pCaMKII alpha expression in the hippocampus, but i.p. injections of acetic acid did not. pERK1/2 expression was also increased by i.t. injection of glutamate, TNF-alpha, and IL-1 beta but not by s.c. injections of formalin or i.p. injections of acetic acid. In an immunohistochemical study, we found that increased pCaMKII alpha and pERK expressions were mainly located at CA3 or the dentate gyrus of the hippocampus. In a behavioral study, we assessed the effects of PD98059 (a MEK 1/2 inhibitor) and KN-93 (a CaMKII inhibitor) following i.c.v. administration on the nociceptive behaviors induced by i.t. injections of glutamate, pro-inflammatory cytokines (TNF-alpha or IL-1 beta), and i.p. injections of acetic acid. PD98059 as well as KN-93 significantly attenuated the nociceptive behavior induced by glutamate, pro-inflammatory cytokines, and acetic acid. Our results suggest that (1) pERK alpha and pCaMK-II located in the hippocampus are important regulators during the nociceptive processes induced by s.c. formalin, i.t. glutamate, i.t. pro-inflammatory cytokines, and i.p. acetic acid injection, respectively, and (2) the alteration of pERK and pCaMKII alpha in nociceptive processing induced by formalin, glutamate, pro-inflammatory cytokines and acetic acid was modulated in a different manner. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.