(A) Timecourse of chronic in vivo morphine treatment and intra-PAG infusions. (B to G) show mean ± SEM hindpaw withdrawal latencies in response to a noxious thermal stimulus using the Hargreaves test. Hindpaw withdrawal latency for each animal at each dose/timepoint is the average of two trials on the right hindpaw and two trials on the left hindpaw. (B) Rats treated with 20 mg/kg morphine per day for 6 days (two s.c. injections of 10 mg/kg/day at 9:00 a.m. & 4:00 p.m.) exhibited thermal hyperalgesia, as exhibited by shorter hindpaw withdrawal latencies, relative to the same rats treated with morphine for 1 day and also relative to a separate group of rats treated with saline for 6 days, **p<0.001; (C) dose-response effects of DAMGO infused into the PAG on hindpaw withdrawal latencies in morphine-treated (n=6) and saline-treated (n=5) rats; *p<0.001 DAMGO dose effect relative to the zero dose condition in morphine-treated rats; (D) dose-response effects of GAT211 infused into the PAG on hindpaw withdrawal latencies in morphine-treated (n=6) and saline-treated (n=6) rats; *p<0.05 main effect of morphine; (E) timecourse effects of DAMGO (0.03 ug) infused into the PAG on hindpaw withdrawal latencies in morphine-treated (n=3) and saline-treated (n=4) rats; red asterisk: p<0.02 DAMGO dose effect relative to zero minutes time point in morphine-treated rats, black asterisk: p<0.001 DAMGO dose effect relative to zero minutes time point in saline-treated rats; (F) timecourse effects of DAMGO (0.03 ug) and GAT211 (10 ug) co-infused into the PAG on hindpaw withdrawal latencies in saline-treated rats (n=4); black asterisk: p<0.01 DAMGO effect relative to zero minutes time point, red asterisk: p<0.01 DAMGO+GAT211 effect relative to zero minutes time point; (G) timecourse effects of DAMGO (0.03 ug) and GAT211 (10 ug) co-infused into the PAG on hindpaw withdrawal latencies in morphine-treated rats (n=6); black asterisk: p<0.01 DAMGO effect relative to zero minutes time point, red asterisk: p<0.01 DAMGO+GAT211 effect relative to zero minutes time point.