LAUSR

ABSTRACT Complex regional pain syndrome (CRPS) is an inadequate local response after a limb trauma, which leads to severe pain and autonomic and trophic changes of the affected limb. Autoantibodies directed against human β2 adrenergic and muscarinic M2-receptors (hβ2AR and hM2R) have been described in CRPS-patients previously.We analyzed sera from CRPS-patients for autoantibodies against hß2AR, hM2R and endothelial cells, and investigated the functional effects of purified IgG, derived from 13 CRPS patients, on endothelial cells. Eleven healthy controls, seven radial fracture patients without CRPS, and 10 patients with peripheral arterial vascular disease served as controls.CRPS-IgG, but not control IgG, bound to the surface of endothelial cells (P < 0.001) and to hβ2AR and hM2R (P < 0.05), the latter being reversed by adding β2AR and M2R antagonists. CRPS-IgG led to an increased cytotoxicity and a reduced proliferation rate of endothelial cells, and by adding specific antagonists, the effect was neutralized. Regarding second messenger pathways, CRPS-IgG induced ERK-1/2-, P38-, and STAT1-phosphorylation, while AKT-phosphorylation was decreased at the protein level. In addition, increased expression of adhesion molecules (ICAM-1, VCAM-1) on the mRNA-level was induced by CRPS-IgG, thus inducing a pro-inflammatory condition of the endothelial cells.Our results show that patients with CRPS not only develop autoantibodies against hβ2AR and hM2R, but these antibodies interfere with endothelial cells, inducing functional effects on these in vitro, and thus might contribute to the pathophysiology of CRPS.