Increase of phosphorylation of calcium/calmodulin-dependent protein kinase-II in several brain regions by substance P administered intrathecally in mice.
In the present study, we investigated the role of phosphorylated calcium/calmodulin-dependent protein kinase-II (pCaMK-II) in nociceptive processing at the spinal and supraspinal levels in the substance P (SP)-induced mouse pain model. In the immunoblot assay, intrathecal (i.t.) injection with SP increased the pCaMK-II level in the spinal cord, and an immunohistochemical study showed that the increase of pCaMK-II immunoreactivity mainly occurred in the laminae I and II areas of the spinal dorsal horn. At the supraspinal level, pCaMK-II was increased in the hippocampus and hypothalamus by i.t. SP injection, and an increase of pCaMK-II 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, pCaMK-II immunoreactivity in the locus coelureus of the brain stem was also increased. The nociceptive behavior induced by SP administered either i.t. or intracerebroventricularly (i.c.v.) was attenuated by KN-93 (a CaMK-II inhibitor). Our results suggest that pCaMK-II located at both spinal cord and supraspinal levels is an important regulator during the nociceptive processes induced by SP administered i.t.
Choi
Seong-Soo
SS
Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, 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
Lee
Han-Kyu
HK
Suh
Hong-Won
HW
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D000096926:Benzenesulfonamides
D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D013373:Substance P; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides