Involvement of phosphorylated extracellular signal-regulated kinase in the mouse substance P pain model.
In the present study, we investigated the role of pERK in nociceptive processing at the spinal and supraspinal levels in the substance P (SP)-induced mouse pain model. In the immunoblot assay, intrathecal (it) injection with SP increased pERK level at the spinal cord and an immunohistochemical study showed that increase of pERK immunoreactivity mainly occurred in the lamina I and II areas of the spinal dorsal horn. At the supraspinal level, pERK was increased in hippocampus and hypothalamus by i.t. SP injection, and an increase of pERK immunoreactivity mainly occurred in the dentate gyrus and CA3 region of hippocampus and paraventricular nucleus on hypothalamus. The nociceptive behavior induced by Sub P administered either i.t. or intracerebroventricularly (i.c.v.) was attenuated by PD98059 (a MEK 1/2 inhibitor) in a dose-dependent manner. Our results suggest that pERK located at both spinal cord and supraspinal levels plays as an important regulator during the nociceptive process activated by SP administered it.
Choi
Seong-Soo
SS
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chuncheon, Gangwon-Do, 200-702, South Korea.
Seo
Young-Jun
YJ
Kwon
Min-Soo
MS
Shim
Eon-Jeong
EJ
Lee
Jin-Young
JY
Ham
Young-Ok
YO
Park
Soo-Hyun
SH
Suh
Hong-Won
HW
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013373:Substance P; D048052:Mitogen-Activated Protein Kinase 3