Studies that have investigated both local (skin biopsies or suction blister fluid) and systemic (plasma, serum) levels of cytokines, including TNF-alpha in CRPS, have found local but not systemic proinflammatory cytokine increases.31,35 Future studies should assess the relationship between local and systemic cytokine levels and their relation to disease duration and severity in CRPS. This evidence concerns the gene TNF and complex regional pain syndrome.