NMDA-R1 antisense oligodeoxynucleotides modify formalin-induced nociception and spinal c-Fos expression in rat spinal cord

Il Ok Lee, Rustam Yukhananov, David G. Standaert, Gregory Crosby

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Noxious peripheral stimuli (thermal, mechanical, or chemical) produce long-term adaptations in the sensitivity of central nociceptive neurons to subsequent noxious stimuli. The mechanisms responsible for this central sensitization are multifactorial, but the activation of spinal N-methyl-d-aspartate (NMDA) receptors plays a pivotal role. Using antisense oligodeoxynucleotides, we tested the role of the NR1 subunit of the NMDA receptor in the nociception and expression of the immediate early gene c-fos following formalin-induced pain. Rats received NMDA-R1 antisense, sense, or missense oligodeoxynucleotides intrathecally three times over a 48-h interval. The day after the last injection of the oligodeoxynucleotide, the formalin test was performed. Pain-related behavior was quantified by counting the incidence of flinching of the injected paw for 60 min, and the animals were perfused and the spinal cord removed for c-Fos immunohistochemistry 60 min later. Immunopositive cells were counted in the laminae I/II 0 and V of the lumbar enlargement. Treatment with NR1 antisense oligodeoxynucleotide resulted in a marked decrease in flinching. Similarly, the antisense oligodeoxynucleotide virtually abolished formalin-induced expression of c-Fos-like immunoreactivity (Fos-IR) in the spinal cord dorsal horn ipsilateral to injection. In contrast, the corresponding sense or missense oligodeoxynucleotides had no effect on either formalin-evoked behavior or c-Fos immunoreactivity. We conclude that an NR1 antisense oligodeoxynucleotide inhibits both nociceptive behavior and c-fos expression following formalin injection in rats, demonstrating that NR1 plays an important role in the development of noxious stimulation induced c-fos expression in this model.

Original languageEnglish
Pages (from-to)183-188
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume79
Issue number1
DOIs
Publication statusPublished - 2004 Sep 1

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Keywords

  • Antisense oligodeoxynucleotide
  • c-Fos
  • Formalin test
  • Hyperalgesia
  • Intrathecal
  • N-methyl-d-aspartate
  • Nociception
  • Spinal cord

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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