Fig. 3. The pronociceptive effects of wildtype (WT) mouse fracture (FX) serum resolved by 21 weeks post-FX.

WT mice exhibited unilateral hindpaw von Frey allodynia and unweighting at 3 weeks post-FX and these pain behaviors gradually resolved over the ensuing 21 weeks (Fig. 1). To test the hypothesis that pronociceptive autoantibodies persist in the serum of WT FX mice up to18, but not 21 weeks, sera from 3, 18, and 21 week post-FX WT mice were injected into 3 week post-FX muMT mice lacking B cells. Both 3 and 18 week post-FX WT mouse sera (500 ul i.p.) caused increased hindpaw allodynia (A) and unweighting (B) in 3 week post-FX muMT mice, but 21 week post-FX WT serum had no effect on allodynia or unweighting in 3 week post-FX muMT mice. A 2-way repeated measures analysis of variance was performed followed by a Holm-Sidak test for post hoc contrasts. Data are expressed as mean values ± SEM. ##P<0.01, and ###P<0.001 for muMT-FX+WT-3wk FX serum (n=7–10/cohort) and muMT-FX+WT-18wk FX serum (n=7–10/cohort) vs muMT-FX+WT-No FX serum (n=8/cohort) or muMT-FX+WT-21wk FX serum (n=6/cohort). muMT: mice lacking B cells, FX: fracture, No FX serum: serum from WT mice that did not undergo FX, FX serum: serum from 3 week post-FX WT mice, BL: baseline, 3 wkFX: mice that are 3 weeks post-FX