The aims of current study were to develop a tibia fracture CRPS model in mice and utilize this model in SP deficient (Tac1−/−) and in CGRP receptor (RAMP1−/−) deficient mice to directly test the hypothesis that neuropeptide signaling is required for the development of the post-fracture innate immunity responses contributing to the development of pain behavior in the fracture model. This evidence concerns the gene TAC1 and complex regional pain syndrome.