Figure 4. (A) The effect of intraperitoneal (ip) naloxone (1 mg/kg) on the drug effect on injured paw shown in time course of paw withdrawal latency (PWL) after thermal injury (dashed line) and the drug application (shaded bar). Pretreatment with naloxone was given 5 min before the application of 5.0% loperamide (open circle), whereas posttreatment was given 20 min after injury (open square). All points represent mean +/− SEM of five animals. **P < 0.01, *P < 0.05 versus control (C), and [dagger][dagger]p < 0.01 versus 5.0% loperamide treatment. (B) Comparison of the area under the curve (AUC) calculated from A. Pre- and postadministration of naloxone significantly reversed the antihyperalgesic effect of 5.0% loperamide (*P < 0.05 vs. 5.0% loperamide; AI = algesic index).