ER stress contributes to chronic hyperalgesia in sickle mice. After BL pain determination, HbAA-BERK and HbSS-BERK mice were treated with i.p. injection of vehicle (0.2% DMSO in saline) or salubrinal (1 mg/kg/day) for 10 days. Pain measures were recorded 4 h after first injection and every other day during injection and postinjection (Supplementary Fig. S5D). (A) Mechanical hyperalgesia. (B) Heat sensitivity. (C) Cold sensitivity. (D) Deep tissue hyperalgesia. Data are mean ± SEM of eight mice. *p < 0.05, **p < 0.001, and ***p < 0.0001 for each time-point versus BL of corresponding group (one-way ANOVA, Bonferroni) in HbSS-BERK. †p < 0.05, ††p < 0.001 and †††p < 0.0001 for salubrinal versus corresponding vehicle at each time-point in HbSS-BERK (two-way ANOVA, Bonferroni). Mean age of mice (months ± SEM) was 5.3 ± 0.1 for HbAA-BERK vehicle, 5.3 ± 0.3 for HbAA-BERK salubrinal, 5.2 ± 0.5 for HbSS-BERK vehicle, and 5.4 ± 0.4 for HbSS-BERK salubrinal. Sal: salubrinal. DMSO, dimethyl sulfoxide. Color images are available online.