Figure 2.

Inhibiting brain CYP2D reduced the first 30 min of codeine-induced analgesia but had no effect on morphine-induced analgesia. Compared with vehicle pretreatment, propranolol pretreatment (darker bar) resulted in significantly lower analgesia (%MPE; a) and area under the analgesia–time curve (AUC; b) for 0–30 min after codeine administration (n=16/group). Propranolol pretreatment (darker bars) did not result in a difference in analgesic AUC_0–30 min or AUC_{30–60 min} (c) after morphine administration (n=5/group; hatched bars). Compared with vehicle pretreatment, propafenone pretreatment (darker bar) resulted in significantly lower %MPE (d) and analgesic AUC_0–30 min (e) after codeine administration (n=6/group). Propafenone pretreatment (darker bars) did not result in a difference in analgesic AUC_0–30 min or AUC_{30–60 min} (f) after morphine administration (n=5/group; hatched bars). Error bars indicate SEM. A within-animal study design was used; for analgesia–time curves, *p<0.05, **p<0.01, and ***p<0.001 using repeated-measures ANOVA with Bonferroni post hoc. For AUCs, *p<0.05, **p<0.01 using paired t-tests.