Figure 4.

KChIP1 or KChIP2 ASO reduces all Kv4 complex components in the DRGs and induces mechanical hypersensitivity. Rats were intrathecally injected with vehicle, LacZ ASO, KChIP1 ASO, or KChIP2 ASO during D1–D3. A, B, KChIP1 ASO induces bilateral mechanical hypersensitivity during D1–D5. Thermal hypersensitivity was not detected. L, Left side; R, right side. Data are mean ± SEM (n = 6). *p < 0.05, compared with the baseline (BL) on the corresponding side (Tukey's post hoc test after one-way ANOVA). **p < 0.05, compared with the baseline (BL) on the corresponding side (Tukey's post hoc test after one-way ANOVA). ***p < 0.001, compared with the baseline (BL) on the corresponding side (Tukey's post hoc test after one-way ANOVA). C–F, Rats were killed on D4 after ASO treatment. Western blotting was performed using total proteins (C, D) or plasma membrane proteins (E, F) isolated from the bilateral L4–L6 DRGs on D4. KChIP1 ASO treatment reduces Kv4.3, KChIP1, and DPP10 in both protein preparations. G, H, KChIP2 ASO induces bilateral mechanical hypersensitivity during D1–D5. Thermal hypersensitivity was not detected. **p < 0.05, compared with the baseline (BL) on the corresponding side by Tukey's post hoc test after one-way ANOVA. ***p < 0.001, compared with the baseline (BL) on the corresponding side by Tukey's post hoc test after one-way ANOVA. I–K, In rats treated with KChIP2 ASO, Kv4.3-, KChIP1- and KChIP2-IR in L5 DRG neurons were reduced on D4. L, In rats treated with KChIP1 ASO, KChIP2-IR in L5 DRG neurons was also reduced on D4. Data are mean ± SD (n = 3). *p < 0.05, compared with vehicle (normalized to 1; Student's t test). **p < 0.01, compared with vehicle (normalized to 1; Student's t test). ***p < 0.001, compared with vehicle (normalized to 1; Student's t test).