Activation of cutaneous immune responses in complex regional pain syndrome.

Activation of cutaneous immune responses in complex regional pain syndrome.
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DOI:
10.1016/j.jpain.2014.01.490
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发表时间:
2014-05
期刊:
影响因子:
4
通讯作者:
Kingery, Wade S.
Kingery, Wade S.
中科院分区:
医学2区
文献类型:
--
作者:
Birklein, Frank;Drummond, Peter D.;Li, Wenwu;Schlereth, Tanja;Albrecht, Nahid;Finch, Philip M.;Dawson, Linda F.;Clark, J. David;Kingery, Wade S.

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复杂性局部疼痛综合征(CRPS)的发病机制尚不清楚,但在CRPS受累肢体的实验性皮肤水疱液中,TNF-α和IL-6升高,类胰蛋白酶(肥大细胞的标志物)也升高。在CRPS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,从而导致疼痛行为。目前的研究使用CRPS患者皮肤活检来确定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上调的TNF-α、IL-6和类胰蛋白酶的细胞来源。从55例CRPS患者的受累皮肤和对侧镜像部位收集皮肤活检,并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CRPS早期,受影响皮肤中的角质形成细胞被激活,导致增殖、表皮增厚和TNF-α和IL-6表达上调。在慢性CRPS中,受影响皮肤的角质形成细胞增殖减少,表皮变薄。急性CRPS患者在受累皮肤中也有肥大细胞积聚增加,但在慢性CRPS中肥大细胞数量没有增加。
The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but TNF-α and 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 with 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.
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