SCI induces a similar increase in pain-like behaviors of wild-type, EPAC1−/− and EPAC2−/− mice, as revealed by an operant mechanical conflict test. (A) Sex-specific differences in locomotor recovery post-SCI in mice. Gender significantly affected locomotor recovery post-SCI in mice. The BMS experiments were performed weekly after surgery, and significant differences between males and females were observed as early as 2 weeks post-injury. Mice were monitored during 4 min observation sessions, during which their movements were assessed according to the methodology and BMS scale originally published in (Basso et al., 2006). Statistical comparison was made using 2-way repeated measures ANOVA followed by Sidak tests. (B) Behavioral tests were performed on female mice 3–4 weeks after surgery. SCI significantly decreased the total number of crossings across aversive probes in the mechanical conflict device, and (C) increased the latency to the second complete crossing. Data are shown as mean ± SEM. 2-way ANOVA was used for comparisons of total number of crossings as data were parametric. For comparisons of latencies of second complete crossing, unpaired t-test was used to compare wild-type sham to wild-type SCI mice, as well as wild-type SCI mice to EPAC1−/− while Mann-Whitney U test was performed to compare wild-type SCI mice to EPAC1−/− SCI mice. ANOVA, analysis of variance; BMS, Basso Mouse Scale; EPAC, exchange protein activated by cAMP; KO, knock-out; n.s., non-significant; SCI, spinal cord injury; SEM, standard error of the mean.