Figure 4 |. σ_1/2 ligands are anti-allodynic in a model of neuropathic pain.

a, Selectivity of four ligands at σ₁ and σ_2. PD-144418 values from the litrature⁴⁷. b, Response of mice to a von Frey filament after spared nerve injury (SNI). Ligands are compared to their vehicles (PD-144418 30 mg/kg (n = 5) vs. kolliphor (n = 5), one-way ANOVA, F(2, 12) = 7.49, p = 0.008; Z4446724338 20 mg/kg (n = 5) vs cyclodextrin (n = 10), one-way ANOVA, F(2, 22) = 25.12, p = 0.0000021; Z4857158944 20 mg/kg (n = 5) vs cyclodextrin (n = 10), one-way ANOVA, F(2, 17) = 5.10, p = 0.02; Z1665845742 20 mg/kg (n = 5) vs saline (n = 10), one-way ANOVA, F(3, 31) = 6.18, p = 0.002; asterisks define individual group differences to respective vehicle control using Dunnett’s multiple comparisons Post-hoc test; kolliphor vs. PD-144418 30 mg/kg (p = 0.009); cyclodextrin vs. Z4446724338 20 mg/kg (p < 0.001); cyclodextrin vs. Z4857158944 20 mg/kg (p = 0.01); saline vs. Z1665845742 20 mg/kg (p = 0.002); * p < 0.05, ** p < 0.01, *** p < 0.001). Data shown are mean ± SEM. Also see Extended Data Fig. 4a. c, The anti-allodynic effects of σ₂, but not σ₁, ligands peak at 24 hours post-injection (two-way ANOVA; time × treatment interaction: F(8,80) = 2.25, p = 0.03; time: F(2,76) = 5.09, p = 0.009; treatment: F(4,40) = 5.40, p = 0.001; four treatment groups (n = 10) except PD-144418 (n = 5); asterisks define difference between Z4446724338 and saline at 1 hr (p = 0.03), 24 hr (p = 0.008), and 48 hr (p = 0.11) for simplicity; ns = not significant, * p < 0.05, ** p < 0.01). Data shown are mean ± SEM.