Fig. 1.

Voluntary running prevents the development of paclitaxel-induced allodynia and increases markers of cellular proliferation and survival in the dentate gyrus of the hippocampus. (A) Schematic shows timing of experimental procedures in Study 1. Voluntary running began 7 days prior to paclitaxel (4 mg/kg i.p. on day 0, 2, 4 and 6) or vehicle injections. Animals were tested for mechanical and cold hypersensitivity for a period of 20 days followed by perfusion on day 21 post paclitaxel or vehicle injection. BrdU (100 mg/kg i.p.) was administered once daily across 5 consecutive days prior to initiation of dosing with paclitaxel or its vehicle. (B) Running wheel rates did not differ in mice treated with paclitaxel or vehicle. Mice allowed to engage in voluntary exercise did not display hypersensitivities to mechanical (C) or cold (D) stimulation in contrast to sedentary mice without access to running wheels. Voluntary running did not alter responsivity to mechanical or cold stimulation in vehicle-treated animals. Paclitaxel treatment decreased the number of Ki67 (E) but not BrdU (F) labeled cells compared to vehicle treatment in sedentary mice. Voluntary running increased both Ki67 and BrdU expression levels irrespective of chemotherapy treatment condition. *p < 0.05 vs. all other groups, two-way ANOVA followed by Bonferroni post-hoc. Exercise, Ex, indicates subjects exposed to running wheels. Sedentary, S, indicates subjects housed without running wheels. (C,D) Arrows denoting injections (inj) denote timing of paclitaxel or vehicle injection. Horizontal arrow denotes timing of voluntary running. (E,F) *p < 0.05 main effect Exercise vs. Sedentary, ⁺p < 0.05 vs. vehicle, Two-Way ANOVA followed by Bonferroni post-hoc. Data are expressed as mean ± SEM. N = 5–6 per group.