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. Author manuscript; available in PMC: 2019 Sep 1.
Published in final edited form as: Anesthesiology. 2018 Sep;129(3):557–575. doi: 10.1097/ALN.0000000000002332

Figure 7. The effects of stopping exercise on sciatic nerve expression of SP and CGRP and the cutaneous pronociceptive mediators IL-6 and NGF.

Figure 7

Figure 1 illustrates the reoccurrence of allodynia and unweighting in exercised mice after stopping exercise for 2 weeks. In these experiments a cohort of fracture mice (FX+Wheel) were treated with 4 weeks ad lib access to a running wheel, starting at 3 weeks post fracture, then the wheel was removed for 2 weeks and then the animals sacrificed (at 9 weeks post fracture) and the sciatic nerve and skin collected. Control fracture mice not provided access to a running wheel (FX+No Wheel) were sacrificed (at 9 weeks post fracture) and the tissues collected. Sciatic nerve SP and CGRP proteins and hindpaw skin IL-6 and NGF proteins were measured by EIA. Neither SP (A), CGRP (B), IL-6 (C), or NGF (E) protein were up-regulated at 9 weeks post fracture in the untreated fracture mice (FX+No Wheel), compared to nonfractured control mice (Control). Stopping exercise for 2 weeks in the wheel treated fracture mice caused an increased expression of SP (A), CGRP (B), IL-6 (C), and NGF (E) proteins at 9 weeks post fracture. At 9 weeks post fracture there were no differences in baseline hindpaw mechanical allodynia (von Frey thresholds) between fracture mice that were treated with wheel exercise for 4 week and then the wheel was removed for 2 weeks and fracture mice that were never given wheel access (D,F). When either an IL-6 receptor antagonist (TB-2-081) or an anti-NGF antibody (anti-NGF) was injected into the 9 week fracture mice, there was no effect in the fracture mice that had not previously been given wheel access, but both drugs reversed mechanical allodynia in fracture mice that had been given 4 weeks running exercise and then the exercise was discontinued for 2 weeks. Values are means ± SD, n=8. One-way analysis of variance with Bonferroni post hoc testing. * P< 0.05, ** P< 0.01, *** P< 0.001 for FX+No Wheel or FX+Wheel vs Control, # P< 0.05, ## P< 0.01, ### P< 0.001 for FX+Wheel vs FX+No Wheel, $ P< 0.05, $$$ P< 0.001 for FX+Wheel Baseline vs FX+Wheel+TB-2-081.