For instance, rat fracture models of CRPS suggest that substance P and Calcitonin Gene-Related Peptide (CGRP) signaling activate receptors on the surface of keratinocytes, resulting in keratinocyte proliferation, and upregulation of inflammatory mediators such as Interleukin-1 and -6 (IL-1 and IL-6), Nerve Growth Factor (NGF), and Tumor Necrosis Factor-alpha (TNF-α) that lead to pain sensitization (Guo et al. 2012; Li et al. 2010; Wei et al. 2009; Sabsovich et al. 2008). The gene discussed is IL6; the disease is complex regional pain syndrome.