Enhanced δ-opioid receptor-mediated antinociception in μ-opioid receptor-deficient mice

Chunyuan Qiu, Ichiro Sora, Ke Ren, George Uhl, Ronald Dubner

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Inflammatory hyperalgesia was induced in wild-type, heterozygous and μ- opioid receptor knockout mice after an intraplantar injection of complete Freund's adjuvant. μ-Opioid receptor knockout mice exhibited faster recovery from hyperalgesia as compared to heterozygous (P <0.05) and wild-type (P <0.01) mice. Naloxone restored hyperalgesia in all genotypes. Naltrindole (δ- opioid receptor-selective antagonist) partially restored the hyperalgesia only in μ-opioid receptor knockout mice (P <0.001). Nor-binaltorphimine (κ-opioid receptor-selective antagonist) had no effect. The μ-opioid receptor-selective agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO), reduced the hyperalgesia in heterozygous and wild-type but not in μ-opioid receptor knockout mice while U69,593 {(+)-(5α,7α,8β)-N-methyl-N-[7-(1- pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide, κ-opioid receptor- selective} produced similar effects in all mice. The δ-opioid receptor- selective agonists, [D-Pen2, D-Pen5]enkephalin (DPDPE) and deltorphin ([D- Ala2]deltrophin-II), produced significantly greater antihyperalgesia in knockout mice (P <0.05). The findings suggest that μ-opioid receptors may be involved in the persistence of inflammatory hyperalgesia and that a δ- opioid receptor-mediated compensatory mechanism in the absence of the μ- opioid receptor is activated by persistent hyperalgesia. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)163-169
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number2
StatePublished - Jan 10 2000


  • μ-Opioid receptor
  • Inflammation
  • Knockout mice

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology


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