Lack of anti-hyperalgesic effects by systemic administration of antidepressants. Thermal pain threshold was assessed at P1 after control or ICS-treatment, using thermal paw withdrawal tests. (A-D) Results represent the time-course of thermal paw-withdrawal latencies (PWL, in seconds) after a single i.v. injection of antidepressants. (A-D) Each data point in [control + vehicle] and [ICS + vehicle] groups is common. (E) Milnacipran was given i.v. once daily for 5 days, as described in Figure 4. Results represent the basal threshold as the latency to paw-withdrawal from thermal stimuli (PWL, in seconds), just before the daily injection of vehicle or milnacipran. *p < 0.05, vs. vehicle-treated control group; #p < 0.05, vs. vehicle-treated and ICS-exposed groups. Data are expressed as the means ± S.E.M.; 3-6 mice per group.