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

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.