Enhanced delta-opioid receptor-mediated antinociception in mu-opioid receptor-deficient mice

Inflammatory hyperalgesia was induced in wild-type, heterozygous and mu-opi oid receptor knockout mice after an intraplantar injection of complete Freu nd's adjuvant, mu-Opioid receptor knockout mice exhibited faster recovery f rom hyperalgesia as compared to heterozygous (P<0.05) and wild-type (P<0.01 ) mice. Naloxone restored hyperalgesia in all genotypes. Naltrindole (delta -opioid receptor-selective antagonist) partially restored the hyperalgesia only in mu-opioid receptor knockout mice (P<0.001). Nor-binaltorphimine (ka ppa-opioid receptor-selective antagonist) had no effect. The (mu-opioid rec eptor-selective agonist, [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin (DAMGO), r educed the hyperalgesia in heterozygous and wild-type but not in mu-opioid receptor knockout mice while U69,593 {(+)-(5 alpha,7 alpha,8 beta)-N-methyl -N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide, kappa-opi oid receptor-selective) produced similar effects in all mice. The delta-opi oid receptor-selective agonists, [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) and deltorphin ([D-Ala(2)]deltrophin-II), produced significantly greater antih yperalgesia in knockout mice (P<0.05). The findings suggest that mu-opioid receptors may be involved in the persistence of inflammatory hyperalgesia a nd that a delta-opioid receptor-mediated compensatory mechanism in the abse nce of the mu-opioid receptor is activated by persistent hyperalgesia, (C) 2000 Elsevier Science B.V. All rights reserved.