Complex regional pain syndrome (CRPS) presents postinjury with disproportionate pain and neuropathic, autonomic, motor symptoms, and skin texture affection. However, the origin of these multiplex changes is unclear. Skin biopsies offer a window to analyze the somatosensory and vascular system as well as skin trophicity with their protecting barriers. In previous studies, barrier-protective exosomal microRNAs were altered in CRPS. We here postulated that tissue architecture and barrier proteins are already altered at the beginning of CRPS. We analyzed ipsilateral and contralateral skin biopsies of 20 fully phenotyped early CRPS patients compared with 20 age- and sex-matched healthy controls. We established several automated unbiased methods to comprehensively analyze microvessels and somatosensory receptors as well as barrier proteins, including claudin-1, claudin-5, and claudin-19. Meissner corpuscles in the skin were bilaterally reduced in acute CRPS patients with some of them lacking these completely. The number of Merkel cells and the intraepidermal nerve fiber density were not different between the groups. Dermal papillary microvessels were bilaterally less abundant in CRPS, especially in patients with allodynia. Barrier proteins in keratinocytes, perineurium of dermal nerves, Schwann cells, and papillary microvessels were not affected in early CRPS. Bilateral changes in the tissue architecture in early CRPS might indicate a predisposition for CRPS that manifests after injury. Further studies should evaluate whether these changes might be used to identify risk patients for CRPS after trauma and as biomarkers for outcome.

中文翻译：

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急性复杂区域疼痛综合征患者双侧迈斯纳小体和乳头微血管缺陷。

复杂区域疼痛综合征 (CRPS) 表现为损伤后不成比例的疼痛以及神经性、自主性、运动性症状和皮肤纹理影响。然而，这些多重变化的起源尚不清楚。皮肤活检提供了一个分析体感和血管系统以及皮肤营养性及其保护屏障的窗口。在之前的研究中，屏障保护性外泌体 microRNA 在 CRPS 中发生了改变。我们在此假设组织结构和屏障蛋白在 CRPS 开始时就已经发生了改变。我们分析了 20 名完全表型的早期 CRPS 患者的同侧和对侧皮肤活检，并与 20 名年龄和性别匹配的健康对照进行比较。我们建立了几种自动化无偏方法来全面分析微血管和体感受体以及屏障蛋白，包括claudin-1、claudin-5和claudin-19。急性 CRPS 患者皮肤中的迈斯纳小体双侧减少，其中一些患者完全缺乏这些。各组之间的默克尔细胞数量和表皮内神经纤维密度没有差异。 CRPS 患者双侧真皮乳头微血管较少，尤其是有异常性疼痛的患者。角质细胞中的屏障蛋白、真皮神经的神经束膜、施万细胞和乳头微血管在早期 CRPS 中不受影响。早期 CRPS 中组织结构的双侧变化可能表明损伤后出现 CRPS 的倾向。进一步的研究应该评估这些变化是否可用于识别创伤后 CRPS 的风险患者并作为结果的生物标志物。