ACY-257 alleviates mechanical allodynia in the SNI model of peripheral nerve injury and in the CFA model of peripheral inflammation. Numbers on down arrows, indicate the day of drug treatment (DT) initiation. Shaded areas on figures indicate the duration of drug treatment. A significant interaction between day of measurement x treatment was followed by a Holm-Sidak post hoc test. (a) SNI group of male C57BL/6J mice treated with ACY-257 (15 mg/kg i.p. for two days and 20 mg/kg i.p. for a week) show reduction of mechanical allodynia in the Von Frey assay. Drug or vehicle treatment began immediately after SNI baseline measurement (n=6–7, two-way ANOVA followed by Holm—Sidak’s post hoc test, F(2,33)=7.83, *P<0.05). (b) CFA group of male mice treated with ACY-257 (20 mg/kg i.p.) show recovery from mechanical allodynia. Treatment started immediately after baseline measurement (n=7–8, two-way ANOVA followed by Holm—Sidak’s post hoc test, F(2,26)=4.99, *P<0.05). (c) Similarly, the CFA group of female mice treated with ACY-257 (20 mg/kg i.p.) recover from mechanical allodynia. Drug treatment started immediately after CFA baseline measurement [(n=6), two-way ANOVA followed by Holm—Sidak’s post hoc test, F(2,20)=7.49, *P<0.05]