siRNA-mediated CaMKIIα knockdown reduced mechanical and thermal hypersensitivity in EAE. Separate groups of 8 mice received (i.t.) CaMKIIα siRNA (2 μg, every 12 h), scrambled siRNA (2 μg, every 12 h), or vehicle for 3 consecutive days from Day 5 to Day 7 postimmunization. A–D, CaMKIIα knockdown by siRNA significantly reduced clinical scores (A), locomotor impairment (B), mechanical allodynia (C), and thermal hyperalgesia (D). Data are expressed as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 compared with the sham immune group; #p < 0.05, ##p < 0.01, ###p < 0.001 compared with the saline-treated EAE group.