Selective blockade of peripheral delta opioid agonist induced antinociception by intrathecal administration of delta receptor antisense oligodeoxynucleotide

Edward J. Bilsky, Tong Wang, Josephine Lai, Frank Porreca

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Previous studies have shown that intrathecal (i.t.) administration of antisense, but not mismatch, oligodeoxynucleotides (ODNs) to the cloned delta opioid receptor (DOR) can inhibit the antinociceptive actions of i.t. delta (δ), but not mu (μ) or kappa (κ), opioid agonists. As a major portion of spinal opioid receptors are localized on the central terminals of the small afferent fibers, we hypothesized that the effects of antisense ODNs given i.t. might be the result of actions at the level of the cell body in the dorsal root ganglion (DRG). This possibility was investigated by assessing the antinociceptive actions of an i.t. or intrapaw (ipaw) administered μ (morphine), δ ([D-Ala2, Glu4]deltorphin) or κ (CI977) opioid agonist in rats treated with i.t. saline or antisense or mismatch ODNs to the DOR (12.5 μg, twice-daily for 3 days). The opioid agonists produced significant antinociception in the 5% formalin-flinch test following either i.t. or ipaw administration. DOR antisense ODN treatment blocked the antinociceptive actions of both i.t, or ipaw [D-Ala2,Glu4]deltorphin without affecting the antinociceptive actions of i.t. or ipaw, morphine or CI977. Radioligand binding studies with [3H]naltrindole (NTI), a δ selective antagonist, indicated an approximate 50% decrease in δ opioid receptors in the lumbar spinal cord following i.t. DOR antisense, but not mismatch, ODN treatment. DOR antisense or mismatch ODN treatment did not affect υ or κ radioligand binding in lumbar spinal cord. These data suggest the possibility that peripheral proteins can be targeted with i.t. antisense ODNs providing significant opportunities for the exploration of the physiological and pathological significance of these substances.

Original languageEnglish (US)
Pages (from-to)155-158
Number of pages4
JournalNeuroscience Letters
Volume220
Issue number3
DOIs
StatePublished - Dec 20 1996

Keywords

  • Delta opioid receptor
  • Dorsal root ganglion
  • Oligodeoxynucleotides

ASJC Scopus subject areas

  • Neuroscience(all)

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