Involvement of phosphorylated Ca2+/calmodulin-dependent protein kinase II and phosphorylated extracellular signal-regulated protein in the mouse formalin pain model.
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-IIalpha level in the spinal cord, and an immunohistochemical study showed that the increase of pERK and pCaMK-IIalpha 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-IIalpha was increased in the hippocampus and hypothalamus by s.c. formalin injection, and an increase of pCaMK-IIalpha 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.
Choi
Seong-Soo
SS
Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okcheon-Dong, Chuncheon, Gangwon-Do, 200-702, South Korea.
Seo
Young-Jun
YJ
Shim
Eon-Jeong
EJ
Kwon
Min-Soo
MS
Lee
Jin-Young
JY
Ham
Young-Ok
YO
Suh
Hong-Won
HW
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002490:Central Nervous System / Q000166:cytology / Q000201:enzymology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D009434:Neural Pathways / Q000166:cytology / Q000201:enzymology*; D010146:Pain / Q000201:enzymology* / Q000503:physiopathology; D010147:Pain Measurement; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D020671:Posterior Horn Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D004791:Enzyme Inhibitors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases