(A) Mechanical sensitization. Paw withdrawal thresholds (g, mean ± SEM) in response to mechanical stimulation with dynamic von Frey filaments were measured before CCI surgery (baseline), on day 7 after surgery before drug administration and for 4 hours after drug injection. HZ166 (1 [▼, ▽], 5 [◆, ◇], 16 [■, □], 48 [▲, △], 160 [, ], 480 [ , ] mg / kg body weight) or vehicle (●, ○) were injected i.p.. Filled symbols, ipsilateral paw; open symbols, contralateral paw. n = 6 mice per group. (B) Dose response curve. Percent maximum possible effect (% MPE) determined at 1 hours after drug application versus dose, mean ± SEM. ANOVA followed by Scheffe’s post hoc test, F (9, 41) = 28.04; P < 0.001 ·, P < 0.05; ***, P < 0.001. (C) Brain concentrations of HZ166 (○, left axis) and antihyperalgesic effects on mechanical hyperalgesia (●, right axis) were measured after the i.p. administration of 48 mg / kg. Data are expressed as mean ± SEM. n = 3 mice per time point. (D) Thermal hyperalgesia. Paw withdrawal latencies (s, mean ± SEM) in response to a defined radiant heat stimulus. Left: time course. On day 7 after CCI surgery, HZ166 (▼, ▽, 16 mg / kg body weight) or vehicle (●, ○) were injected i.p. and paw withdrawal latencies were monitored for 3 hours after injection. n = 6 mice per group. Right: statistical analysis. AUC (g·h, mean ± SEM). **, P < 0.01 (unpaired t-test).