Increase of phosphorylation of calcium/calmodulin-dependent protein kinase-II in several brain regions by substance P administered intrathecally in mice

Brain Res Bull. 2005 May 15;65(5):375-81. doi: 10.1016/j.brainresbull.2005.01.016.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Benzylamines / pharmacology
  • Blotting, Western / methods
  • Brain / anatomy & histology
  • Brain / drug effects*
  • Brain / enzymology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Enzyme Inhibitors / pharmacology
  • Immunohistochemistry / methods
  • Male
  • Mice
  • Mice, Inbred ICR
  • Pain Measurement / drug effects
  • Phosphorylation / drug effects
  • Spinal Cord / drug effects
  • Spinal Cord / enzymology
  • Substance P / administration & dosage
  • Substance P / pharmacology*
  • Sulfonamides / pharmacology
  • Time Factors

Substances

  • Benzylamines
  • Enzyme Inhibitors
  • Sulfonamides
  • KN 93
  • Substance P
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases