Fig. 3

Neuropeptide signaling is crucial for the development of post fracture pronociceptive serum effects. When serum from 3 week post fracture wildtype fracture mice (WT-FX) was injected into 3 week post fracture muMT fracture mice (muMT-FX), the mice gradually developed increased hind paw von Frey allodynia (a) and unweighting (b) over the ensuing week that is resolved by 2 weeks post-injection, as compared with muMT mice receiving wildtype no fracture (WT-NO FX) mouse serum. When serum from fracture mice treated with the substance P (SP) tachykinin 1 receptor antagonist LY303870 for 7 days (WT-FX-LY) was injected in to the muMT-FX mice, there was no pronociceptive effect. Similarly, when serum from 3-week post fracture mice lacking SP (Tac1^−/−-FX) or the calcitonin gene-related peptide receptor (RAMP1^−/−-FX) was injected into 3-week post fracture muMT-FX mice, there was no effect on hind paw allodynia (a) and unweighting (b). Data were analyzed using a two-way repeated measures analysis of variance (ANOVA) with Bonferroni correction test for post hoc contrasts, data are expressed means ± SEM, n = 8–10 per cohort. ^###P < 0.001 for muMTFX-FX + WT-FX serum vs muMT-FX + WT-NO FX serum