Fig. 2

Neuropeptide signaling is required for post fracture immunoglobulin M (IgM) deposition in the skin, sciatic nerve, and spinal cord. IgM protein levels in mouse hind paw skin, sciatic nerve, and spinal cord at 3 weeks after fracture were determined by Western blot analysis. Compared to control wildtype no fracture mice (WT-NO FX), IgM levels in the skin, sciatic nerve, and spinal cord from wildtype fracture mice (WT-FX) were dramatically increased at 3 weeks post fracture (a–f). Treating fracture mice with the substance P tachykinin1 receptor antagonist LY303870 (FX + LY) for 7 days just prior to cast removal reversed IgM-antigen complex deposition in all tissues (a–c). IgM levels in skin, sciatic nerve, and spinal cord were also elevated in the CGRP receptor-deficient fracture mice (RAMP1^−/−-FX) at 3 weeks post fracture compared with WT-NO FX control mice, but this increase was attenuated compared to the increase observed in the WT-FX mice (d–f). Data were analyzed using a one-way analysis of variance (ANOVA) with Bonferroni correction test for post hoc contrasts, data are expressed means ± SEM, n = 6 per cohort. ***P < 0.001 vs. control WT-NO FX, ^###P < 0.001 for FX + LY or RAMP1^−/−-FX vs WT-FX