Pain responses to radiant heat (light) at 30 and 60 min after acute subcutaneous administration of morphine in 20-day-old previously opioid-naive rats or previously treated with 3 days of twice-daily escalating morphine doses to become opioid-tolerant. (A) Grouped values for area under the curve (AUC) of the delay in paw withdrawal from heat (latency), over the 60 min time of postmorphine testing (postmorphine latencies measured at 30 and 60 min minus premorphine latency). Maximum heat exposure was 10 s to prevent tissue damage. (B) Group results of paw withdrawal latency before and then 30 and 60 min after acute administration of 3 mg/kg morphine in 22 opioid-naive rats and 15 mg/kg morphine in 12 opioid-tolerant rats. Similar AUC for the two groups indicates an approximately fivefold increase in the analgesic dose response produced by the previous morphine treatment in the opioid-tolerant group. ^*Significant differences between morphine-naive versus morphine-tolerant groups at various doses (P < 0.05, between-group ANOVA with the Student’s Newman–Keuls test for post hoc analyses).