Blocking spinal α2 receptors reduces the antinociceptive effect of supraspinal gabapentin (GP). (A) After SNI, the mechanical withdrawal threshold of the injured paw differs significantly from its preinjury baseline level (**P < 0.01). Supraspinal GP (50 μg i.c.v.) increased the withdrawal threshold, demonstrating its antinociceptive effect. Intrathecal saline (n = 8) had no effect on the antinociceptive action of supraspinal GP (open black bars compared with filled red bars, ****P < 0.0001); i.t. yohimbine (5 μg, n = 8) reduced the antinociceptive effect of GP (open black bars compared with filled red bars, n.s., 2-way RM-ANOVA, the Sidak multiple comparison test; df = 14). (B) Supraspinal GP and i.t. yohimbine did not alter mechanical thresholds of the contralateral, uninjured paw. Data are mean ± SEM. ANOVA, analysis of variance; i.c.v., intracerebroventricular; i.t., intrathecal; n.s., not significant; RM-ANOVA, repeated-measures analysis of variance; SNI, spared nerve injury.