Fig. 7.
AAV9-NaV1.7-CRS reverses paclitaxel-induced mechanical and cold allodynia. (A) The paw withdrawal threshold of male and female mice was measured at different time points [Baseline: time 0 (pre injection); and Day 7, 14, 16, and 21] after 4 intraperitoneal injections of paclitaxel (8 mg/kg, i.p.). Mice were treated intrathecally (i.t.) with AAV9-SCR or AAV9-NaV1.7-CRS (1 × 1010 viral particles in 5 µL) as indicated. Results were compared using three-way ANOVA with time, treatment, and virus as factors and post hoc Holm-Šídák test; *P < 0.05 Pac-AAV9-SCR vs. Veh + AAV9-SCR; &P < 0.05 Pac-AAV9-NaV1.7-CRS vs. Veh + AAV9-NaV1.7-CRS; #P < 0.05 Pac-AAV9-NaV1.7-CRS vs. Pac-AAV9-SCR). Detailed statistical analysis is in Dataset S1. (B) Area under the curve in A. Statistical significance as indicated (One-way ANOVA with Tukey’s post hoc test). Taken together, the data show that AAV9-NaV1.7-CRS reversed CIPN-induced mechanical allodynia. (C) Time of aversive responses for male and female mice was measured at different time points [Baseline: time 0 (before any injection); and Day 8, 15, 17, and 22] after 4 intraperitoneal injections of paclitaxel (8 mg/kg, i.p.). Mice were treated intrathecally (i.t.) with AAV9-SCR or AAV9-NaV1.7-CRS (1 × 1010 viral particles in 5 µL) as indicated. Results were compared using three-way ANOVA with time, treatment, and virus as factors and post hoc Holm-Šídák test; *P < 0.05 Pac-AAV9-SCR vs. Veh + AAV9-SCR; &P < 0.05 Pac-AAV9-NaV1.7-CRS vs. Veh + AAV9-NaV1.7-CRS; #P < 0.05 Pac-AAV9-NaV1.7-CRS vs. Pac-AAV9-SCR). Detailed statistical analysis is in Dataset S1. (D) Area under the curve in C. Statistical significance as indicated in the figure (one-way ANOVA with Tukey’s post hoc test). Taken together, the data show that AAV9-NaV1.7-CRS reversed CIPN-induced cold allodynia (acetone test) in both male and female mice. n = 8 animals; error bars indicate mean ± SEM; detailed statistical analysis is in Dataset S1. The experiments were conducted by investigators blinded to treatments.