All animals received a plantar incision on the left hindpaw. Metformin (30, 100, 150 or 200 mg/kg) or vehicle was injected IP for 4 consecutive days, starting 2 days prior to surgery, the day of surgery, and 1 day post-incision surgery and animals assessed for mechanical sensitivity by von Frey hair stimulation at the indicated time points. A) Metformin (30, 100, 150 or 200 mg/kg) injection dose-dependently inhibited plantar incision-induced acute mechanical hypersensitivity (area over vehicle curve shown in B) and (C) hyperalgesic priming precipitated by PGE2 (100 ng) in the left hindpaw on day 14 after incision (area over vehicle curve shown in D). Behavioral data was analyzed by two-way ANOVA with Bonferroni post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001 (n = 6 per group except metformin 150 mg/kg, n = 8).