Fig. 2.

Dose response studies for hydromorphone were performed using standard (left panel) and cumulative dose response protocols (right panel) as described in the methods. For the standard dose response protocol, individual groups of mice (N=5–8/dose) were injected with a single dose of hydromorphone s.c. and tested for antinociception 45 min later. For the cumulative dose response protocol, mice (N=8) were injected with a starting dose of hydromorphone s.c. and tested for antinociception 45 min later. Mice that were not analgesic (i.e., tail flick latency< 10 s), were injected with another dose (see Methods) and retested. This cumulative dosing was continued until all mice were analgesic. The data presented are the combined results of five independent experiments for both cumulative and standard dosing protocols .The mean ED₅₀ (95% CL) for the standard dosing experiments was 0.22 mg/kg (0.20–0.24 mg/kg). The mean ED₅₀ (95% CL) for the cumulative dosing experiments was 0.37 mg/kg (0.31–0.43 mg/kg).