Ifenprodil induced antinociception and decreased the expression of NR2B subunits in the dorsal horn after chronic dorsal root ganglia compression in rats

Anesth Analg. 2009 Mar;108(3):1015-20. doi: 10.1213/ane.0b013e318193ffd2.

Abstract

Background: Spinal N-methyl D-aspartate receptors play an important role in the pathogenesis of neuropathic pain, and administration of N-methyl D-aspartate receptor antagonists can attenuate this hyperpathia. Ifenprodil is an antagonist selective for N-methyl D-aspartate receptor 2B (NR2B) subunits. Several researches have reported effective analgesia of ifenprodil in animal models of neuropathic pain. We extended this work to include chronic compression of the dorsal root ganglia (CCD).

Methods: The paw withdrawal mechanical threshold and paw withdrawal thermal latency tests were used to assess mechanical allodynia and thermal hyperalgesia after a CCD operation and intrathecal injection of ifenprodil. We used immunohistochemistry and immunoblotting to investigate the effect of ifenprodil on NR2B subunits expression in CCD rats.

Results: The data revealed increased expression of NR2B subunits in the superficial dorsal horn in CCD rats. We found that, in addition to a marked suppression of thermal hyperalgesia and mechanical allodynia, intrathecal injection ifenprodil treatment causes a decreased expression of NR2B in the spinal cord.

Conclusions: These data suggest that ifenprodil induced antinociception in CCD rats and provided further evidence for the important role of NR2B subunits in the development of neuropathic pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics*
  • Animals
  • Behavior, Animal / drug effects
  • Blotting, Western
  • Electrophoresis, Polyacrylamide Gel
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Immunohistochemistry
  • Injections, Spinal
  • Male
  • Nerve Compression Syndromes / metabolism*
  • Nerve Compression Syndromes / pathology
  • Pain Measurement / drug effects
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / biosynthesis*

Substances

  • Analgesics
  • Excitatory Amino Acid Antagonists
  • NR2B NMDA receptor
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • ifenprodil