Antagonism of locally-administered loperamide–oxymorphindole. Paw withdrawal thresholds using the Hargreaves assay were measured for naïve animals, inflamed animals, and animals treated with an intraplantar injection of 0.3 nmol loperamide and oxymorphindole. (A) Ability of β-funaltrexamine, an irreversible μ-opioid receptor antagonist, to inhibit loperamide–oxymorphindole antihyperalgesia. Three different doses of β-funaltrexamine were given 24 h before loperamide-oxymorphindole as an intraplantar injection. (B) Ability of naltrindole, a δ-opioid receptor antagonist, to inhibit loperamide–oxymorphindole antihyperalgesia. Increasing doses of naltrindole were given concurrently with 0.3 nmol of loperamide–oxymorphindole as an intraplantar injection. (C) Ability of naloxone methiodide, a peripherally-restricted opioid antagonist, to inhibit loperamide–oxymorphindole antihyperalgesia. Increasing doses of naloxone methiodide were given concurrently with 0.3 nmol loperamide–oxymorphindole as an intraplantar injection. (A–C) Paw withdrawal thresholds were measured using the Hargreaves assay and antagonist data were compared to 0.3 nmol loperamide–oxymorphindole using ordinary one-way ANOVA with Bonferroni test for multiple comparisons. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. CFA, complete Freund’s adjuvant; PWL, paw withdrawal latency.