Effect of treadmill training and spinal cord injury (SCI) on mechanical sensitivity assessed by von Frey filaments and a place escape/avoidance paradigm. (A) SCI-induced mechanical hypersensitivity to light filaments (0.16 g) is significantly ameliorated by sensorimotor activity (###p < 0.001 comparing SCI with sham animals; ***p < 0.001, ****p < 0.0001 comparing trained (SCI+T) with untrained SCI mice). (B) No overall group differences are observed with the 0.4 g filament, but changes over time. (C, D) Stronger filaments reveal a significant hypo-responsiveness comparing SCI with sham mice irrespective of training (#p < 0.05; ###p < 0.001; #### p < 0.0001, comparing SCI with sham animals irrespective of training). (E) Graphical representation of the place escape/avoidance (PEAP) set-up. Animals are freely moving in a box consisting of a dark and a light side placed on a wire mesh screen. After a 10 min exploration phase (no stimulus), mice are stimulated with the 0.16 g von Frey filament when present on the dark side of the chamber in a 3 × 5 min test phase. (F) Analysis of the time spent on the dark side reveals no significant difference between treadmill trained SCI (SCI+T) and sham mice (Sham; Sham+T). In contrast, untrained SCI mice spent significant less time on the dark side compared with sham and trained SCI mice to avoid the light mechanical stimulus (two-way analysis of variance, p < 0.001 for group differences; protected least significant difference **p < 0.01; ****p < 0.0001).