p38/MAPK inhibitor modulates the expression of dorsal horn GABA(B) receptors in the spinal nerve ligation model of neuropathic pain

Neuroimmunomodulation. 2011;18(3):150-5. doi: 10.1159/000323141. Epub 2011 Jan 18.

Abstract

Background: Neuropathic pain is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent studies have suggested that activated microglia in spinal cord may play a vital role in nerve injury-induced neuropathic pain, but the exact mechanisms have not been fully determined.

Methods: First, we investigated the changes of dorsal horn GABA(B) receptor 1 (R1) expression in spinal nerve ligation rats. Second, we explored whether activated microglia contributed to such neuron changes by intrathecal administration of the p38 inhibitor, SB203580.

Results: In this study, we found a dynamic change of GABA(B)R1a protein expression after spinal nerve ligation, and the peripheral nerve injury-induced downregulation of GABA(B)R1a expression in the spinal dorsal horn could be prevented by intrathecal administration of a p38/MAPK inhibitor SB203580.

Conclusions: Our results provide valuable information for a better understanding of neuropathic pain and may contribute to developing effective treatments in future studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Down-Regulation / physiology
  • Gliosis / chemically induced
  • Gliosis / enzymology
  • Gliosis / metabolism*
  • Ligation / methods
  • Male
  • Microglia / drug effects
  • Microglia / enzymology
  • Microglia / metabolism*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / enzymology*
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / biosynthesis*
  • Receptors, GABA-B / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Protein Kinase Inhibitors
  • Receptors, GABA-B
  • p38 Mitogen-Activated Protein Kinases