Allodynia and hyperalgesia produced by specific inhibition of spinal C-fos expression: Lack of correlation with dynorphin content

Mohab M. Ibrahim, Heriberto P. Mata, Monica Chawla, Josephine Lai, Frank Porreca, T. Philip Malan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Inhibition of spinal Fos expression increases formalin-induced nociception and decreases spinal prodynorphin messenger ribonucleic acid (mRNA), suggesting that Fos modulates nociception by inducing dynorphin synthesis. This study tests the hypothesis that Fos modulates sensitivity to other somatic stimuli, such that inhibition of Fos expression will result in tactile allodynia and thermal hyperalgesia. In addition, it correlates the somatosensory effects of inhibition of Fos expression with spinal dynorphin content. Antisense oligodeoxynucleotide (ODN) to c-fos mRNA was administered by intrathecal infusion. Tactile sensitivity was tested by probing the hindpaw with von Frey filaments. Thermal sensitivity was quantitated by using withdrawal latency to radiant heat. Two percent formalin was injected into the dorsal hindpaw, and flinches were quantitated. Fos was quantitated by counting immunoreactive cells. Dynorphin was measured by immunoassay. Intrathecal antisense, but not mismatch, ODN resulted in tactile allodynia, thermal hyperalgesia, and hyperalgesia to formalin-induced nociception. Antisense ODN decreased Fos-like immunoreactivity after formalin injection but did not alter Jun-like immunoreactivity. Antisense ODN had differing effects on spinal dynorphin content, depending on the method of administration. These experiments show a role of Fos in modulating somatosensory sensitivity and suggest that induction of dynorphin synthesis is not the sole mechanism by which Fos does so.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalJournal of Pain
Volume2
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Allodynia
  • Dynorphin
  • Fos
  • Hyperalgesia
  • Opioid
  • Transcription factors

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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