Fig. 5

Metformin attenuated chronic morphine tolerance. Tail-flick method was performed to evaluate the effect of metformin on the morphine tolerance. Data were shown as percentage of maximal possible effect (% MPE). Twelve mice were included in each group. a, c Metformin (50, 100, and 200 mg/kg, i.p.) exhibited no effects on the initial analgesic response to morphine (10 mg/kg, s.c.) (n = 8). b, d Metformin suppressed chronic morphine tolerance (n = 8) (*p < 0.05; **p < 0.01; Bonferroni’s post hoc tests). Metformin was administered intraperitoneally daily 15 min before each morphine injection