Using the mouse and rat fracture-cast immobilization models of CRPS, it has been shown that facilitated release of neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) from sensory C-fibers [8] leads to inflammation and pain sensitization by the activation of neuropeptide receptors on keratinocytes stimulating expression of high levels of inflammatory cytokines (TNF, IL-1, IL-6) and nerve growth factor (NGF) [8, 10–13], and on mast cells, inducing degranulation [14]. The gene discussed is NGF; the disease is complex regional pain syndrome.