Differential efficacy of intrathecal NMDA receptor antagonists on inflammatory mechanical and thermal hyperalgesia in rats

Aldric Hama, Jeung Woon Lee, Jacqueline Sagen

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Spinal cord dorsal horn N-methyl-D-aspartate (NMDA) receptors have been implicated in central sensitization, enhanced responsiveness to peripheral stimuli following peripheral injury. Since hyperalgesia is a behavioral consequence of central sensitization, it should be attenuated at the level of the dorsal horn with NMDA receptor antagonists. However, responsiveness to thermal and mechanical hyperalgesia may be distinct, and have thus far not been directly compared in chronic inflammatory pain models. In the present study, inflammation was induced with complete Freund's adjuvant (CFA) injected into the rat hind paw and NMDA receptor antagonists dizocilpine (MK-801) or 2-amino-5-phosphonovaleric acid (AP-5) were intrathecally injected in rats to determine the effects on both mechanical and thermal hyperalgesia. Locomotor tests and reflexes were also conducted to evaluate potential motor side effects. The NMDA receptor antagonists dose-dependently ameliorated mechanical hyperalgesia, but had marginal effects on thermal hyperalgesia. In ranges near antihyperalgesic doses, significant disruption of motor coordination was observed for both antagonists. These results suggest that, depending on the stimulus, NMDA receptors may have variable significance for central sensitization-mediated hyperalgesia, and that NMDA receptor antagonists may have therapeutic potential for some, but not all components in the clinical manifestation of inflammatory pain.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalEuropean Journal of Pharmacology
Volume459
Issue number1
DOIs
StatePublished - Jan 10 2003

Keywords

  • Central
  • NMDA (N-methyl-D-aspartate)
  • Pain
  • Sensitization
  • Spinal cord

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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