CaMKIIα inhibition by prophylactic KN93 administration reduced clinical symptoms and attenuated hyperalgesia in EAE. Separate groups of eight mice were treated with KN93 (45 nmol, i.t.) or saline from Day 1 to Day 8 along with the immunization with MOG35-55 on Day 0 to induce EAE. A–D, Prophylactic KN93 administration (45 nmol, i.t.) significantly attenuated clinical symptoms (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.