Activation of cutaneous immune responses in complex regional pain syndrome

The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but tumor ne- crosis factor alpha (TNF-a) and interleukin-6 (IL-6) are elevated in experimental skin blister fluid from CRPS-affected limbs, as is tryptase, a marker for mast cells. In the rat fracture model of CRPS, exag- gerated sensory and sympathetic neural signaling stimulate keratinocyte and mast cell proliferation, causing the local production of high levels of inflammatory cytokines leading to pain behavior. The current investigation used CRPS patient skin biopsies to determine whether keratinocyte and mast cell proliferation occur in CRPS skin and to identify the cellular source of the up-regulated TNF-a, IL-6…