Naloxone-mediated induction of MOR and DOR functional competence in vivo. Rats received injections (intraplantar, 50 µl) of either vehicle (VEH), naloxone (NAL, 0.4 μg), 6β-naltrexol (6βNTX; 4 μg) or NAL + 6βNTX, 85, 65, and 45 minutes before receiving an injection (intraplantar, 50 µl) of PGE2 (0.3 µg) with either DAMGO (8 µg) or DPDPE (20 µg). Paw withdrawal latency (PWL) in response to a thermal stimulus applied to the ventral surface of the hind paw was measured in duplicate before (baseline) and at 5-minute intervals after the PGE2/opioid injection for 20 minutes. Data are expressed as the change in PWL from baseline responses and represent the mean ± S.E.M. of 4–6 rats per group (for some data points, error bars are contained within the size of the symbol). Baseline PWL averaged 9.8 ± 0.4 seconds and was not altered by pretreatment with either naloxone or 6β-naltrexol alone or in combination (Supplemental Fig. 4). *P < 0.05, **P < 0.01, ***P < 0.001 compared with VEH pretreatment group.