Substance P–deficient (SP KO) and CGRP RAMP1 receptor–deficient (RAMP1 KO) fracture (FX) mice had reduced hind paw allodynia, unweighting, warmth, and edema, compared with wild-type (WT) fracture mice. WT fracture mice exhibited hind paw von Frey allodynia (A), unweighting (B), warmth (C), and edema (D) at 3 weeks after fracture. The SP-deficient fracture mice had attenuated hind paw allodynia (A) and unweighting (B), and failed to develop hind paw warmth (C) or edema (D). Similarly, the RAMP1 receptor–deficient fracture mice had no von Frey allodynia (A), attenuated unweighting (B), and no warmth (C), but the development of postfracture hind paw edema was unaffected by the loss of calcitonin gene–related peptide signaling (D), compared with WT FX mice. Values are mean ± SE, n = 8 per cohort. One-way analysis of variance (P < 0.001) with Bonferroni post hoc testing **P < 0.01 and ***P < 0.001 for WT FX, SP KO FX, or RAMP1 KO FX vs WT control, ##P < 0.01 and ###P < 0.001 for SP KO FX, or RAMP1 KO FX vs WT FX.