Calcitonin gene–related peptide and substance P are released from the cytokine-sensitized nociceptors (neurogenic inflammation) and cause reddening, warmth, and edema36,96; substance P further promotes hair growth,71 and calcitonin gene–related peptide enhances sweating.80 Throughout the course of CRPS, most of these signs normalize, which demonstrates some change in pathophysiology.54 Recent investigations suggest a contribution of the adaptive immune system as well. This evidence concerns the gene TAC1 and complex regional pain syndrome.