Figure 1. Pharmacological blockade of Na_V1.1 is antinociceptive.

Systemic administration of Compound B (comp B; 60 mg/kg) has no effect on baseline mechanical thresholds of naive mice (baseline, 0.760 ± 0.03 g, vs. Compound B, 0.836 ± 0.105 g, 2-way ANOVA, P = 0.501, n = 7). Three days after spared nerve injury (SNI), mice exhibit mechanical hypersensitivity (~57%) ipsilateral to the injury (baseline, 0.760 ± 0.03 g, vs. SNI, 0.330 ± 0.034 g, 2-way ANOVA, P = 0.0001). A systemic injection of a single dose of Compound B (i.p., 60 mg/kg) significantly reduces mechanical hypersensitivity 30 minutes (i.p., 60 mg/kg; 0.515 ± 0.072 g, 2-way ANOVA, P = 0.039, n = 7), but not 15 minutes after injection. Contralateral mechanical thresholds were unaffected by the compound (0.703 ± 0.051 g). One month after SNI, mice still exhibited mechanical hypersensitivity ipsilateral to the injury. Again, a single dose of Compound B (i.p., 60 mg/kg) significantly reduced mechanical hypersensitivity (60 minutes; SNI baseline, 0.277 ± 0.031 g, vs. Compound B, 0.530 ± 0.061 g, 2-way ANOVA, P = 0.003, n = 7). Data are presented as mean ± SEM with *P ≤ 0.05 and **P ≤ 0.005.