Birklein Frank, Drummond Peter D, Li Wenwu, Schlereth Tanja, Albrecht Nahid, Finch Philip M, Dawson Linda F, Clark J David, Kingery Wade S
Department of Neurology, University Medical Center, Mainz, Germany.
School of Psychology and Exercise Science, Murdoch University, Perth, Australia.
J Pain. 2014 May;15(5):485-95. doi: 10.1016/j.jpain.2014.01.490. Epub 2014 Jan 23.
The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but tumor necrosis factor alpha (TNF-α) 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, exaggerated 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-α, IL-6, and tryptase observed in CRPS experimental skin blister fluid. Skin biopsies were collected from the affected skin and the contralateral mirror site in 55 CRPS patients and the biopsy sections were immunostained for keratinocyte, cell proliferation, mast cell markers, TNF-α, and IL-6. In early CRPS, keratinocytes were activated in the affected skin, resulting in proliferation, epidermal thickening, and up-regulated TNF-α and IL-6 expression. In chronic CRPS, there was reduced keratinocyte proliferation, leading to epidermal thinning in the affected skin. Acute CRPS patients also had increased mast cell accumulation in the affected skin, but there was no increase in mast cell numbers in chronic CRPS.
The results of this study support the hypotheses that CRPS involves activation of the innate immune system, with keratinocyte and mast cell activation and proliferation, inflammatory mediator release, and pain.
复杂性区域疼痛综合征（CRPS）的发病机制尚未明确，但在CRPS患肢的实验性皮肤水疱液中，肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）水平升高，肥大细胞标志物类胰蛋白酶也是如此。在CRPS的大鼠骨折模型中，过度的感觉和交感神经信号刺激角质形成细胞和肥大细胞增殖，导致局部产生高水平的炎性细胞因子，进而引发疼痛行为。本研究采用CRPS患者的皮肤活检样本，以确定CRPS皮肤中是否发生角质形成细胞和肥大细胞增殖，并确定在CRPS实验性皮肤水疱液中观察到的TNF-α、IL-6和类胰蛋白酶上调的细胞来源。收集了55例CRPS患者患侧皮肤和对侧镜像部位的皮肤活检样本，对活检切片进行角质形成细胞、细胞增殖、肥大细胞标志物、TNF-α和IL-6的免疫染色。在早期CRPS中，患侧皮肤中的角质形成细胞被激活，导致增殖、表皮增厚以及TNF-α和IL-6表达上调。在慢性CRPS中，角质形成细胞增殖减少，导致患侧皮肤表皮变薄。急性CRPS患者患侧皮肤中的肥大细胞积聚也增加，但慢性CRPS患者的肥大细胞数量没有增加。
本研究结果支持以下假说，即CRPS涉及先天性免疫系统的激活，伴有角质形成细胞和肥大细胞的激活与增殖、炎性介质释放以及疼痛。
