Figure 5: Topically administered loperamide-oxymorphindole synergizes in inflamed animals.
A) Peripherally mediated thermal nociceptive responses in the Hargreaves assay were assessed. Subjects were given a topical solution of loperamide, oxymorphindole or combination on the inflamed hindpaw and post-drug responses are shown as % anti-hyperalgesia, which was used to generate concentration-response curves. B) Isobolographic analysis of the data from A, showing a synergistic interaction compared to the theoretical additive value. **** p<0.0001. C) Anti-hyperalgesic tolerance to repeated administrations of topical loperamide-oxymorphindole was assessed. Subjects were given twice daily topical treatments of either vehicle or 15 μM loperamide-oxymorphindole for 3 days. On the fourth day, all animals received increasing concentrations of loperamide-oxymorphindole to generate cumulative dose-response curves.