Involvement of phosphorylated Ca2+/calmodulin-dependent protein kinase II and phosphorylated extracellular signal-regulated protein in the mouse formalin pain model

被引:53
作者
Choi, Seong-Soo
Seo, Young Jun
Shim, Eon Jeong
Kwon, Min-Soo
Lee, Jin-Young
Ham, Young-Ok
Suh, Hong-Won
机构
[1] Hallym Univ, Coll Med, Dept Pharmacol, Chunchon 200702, Gangwon Do, South Korea
[2] Hallym Univ, Coll Med, Inst Nat Med, Gangwon Do 200702, South Korea
关键词
phospho-CaMKII; phospho-ERK; formalin; nociceptive behavior; spinal cord; hippocampus; hypothalamus; intrathecal; intracerebroventricular;
D O I
10.1016/j.brainres.2006.06.048
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the present study, we investigated the role of phosphorylated calcium/calmodulin-dependent protein kinase II (pCaMK-II) and phosphorylated extracellular signal-regulated protein kinase (PERK) in nociceptive processing at the spinal and supraspinal levels in the formalin subcutaneous induced mouse pain model. In the immunoblot assay, subcutaneous (s.c.) injection with formalin increased the pERK and pCaMK-II alpha level in the spinal cord, and an immunohistochemical study showed that the increase of pERK and pCaMK-IIa immunoreactivity mainly occurred in the laminae I and II areas of the spinal dorsal horn. At the supraspinal level, although pERK was not changed in the hippocampus induced by formalin s.c. injection, pCaMK-IIa was increased in the hippocampus and hypothalamus by s.c. formalin injection, and an increase of pCaMK-II alpha immunoreactivity mainly occurred in the pyramidal cells and the stratum lucidum/radiatum layer of the CA3 region of hippocampus and paraventricular nucleus of the hypothalamus. Moreover, pERK immunoreactivity in the hypothalamic paraventricular nucleus was also increased. The second phase of nociceptive behavior induced by formalin administered either i.t. or intracerebroventricularly (i.c.v.) was attenuated by PD98059 (ERK inhibitor) as well as KN-93 (a CaMK-II inhibitor). On the other hand, the first phase of nociceptive behavior induced by formalin s.c. injection was not affected by i.t. KN-93. Our results suggest that pERK and pCaMK-II located at both the spinal cord and supraspinal levels are an important regulator during the nociceptive processes induced by formalin administered s.c. respectively. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:28 / 38
页数:11
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