Orthopaedic Research Institute, Department of Orthopaedic Surgery, St George Hospital Campus, University of New South Wales, Sydney, Australia.
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, UK.
Am J Sports Med. 2018 Mar;46(3):671-678. doi: 10.1177/0363546517741127. Epub 2017 Nov 30.
The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and that signal cell and tissue damage.
To investigate whether the presence of alarmins is higher in patients with idiopathic frozen shoulder than in control subjects.
Controlled laboratory study.
Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients with unstable shoulders (control). The samples were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry using antibodies against alarmin molecules including high-mobility group protein B1 (HMGB1), interleukin 33, S100A8, S100A9, and the peripheral nerve marker PGP9.5. Immunoreactivities were rated in a blinded fashion from "none" to "strong." Immunohistochemical distribution within the capsule was noted. Before surgery, patient-ranked pain frequency, severity, stiffness, and the range of passive shoulder motion were recorded and statistically analyzed.
Compared with control patients, patients with frozen shoulder had greater frequency and severity of self-reported pain ( P = .02) and more restricted range of motion in all planes ( P < .05). H&E-stained capsular tissue from frozen shoulder showed fibroblastic hypercellularity and increased subsynovial vascularity. Immunoreactivity of alarmins was significantly stronger in frozen shoulder capsules compared with control capsules ( P < .05). Furthermore, the expression of the alarmin molecule HMGB1 significantly correlated ( r > 0.9, P < .05) with the severity of patient-reported pain.
This study demonstrates a potential role for key molecular danger signals in frozen shoulder and suggests an association between the expression of danger molecules and the pain experienced by patients.
特发性冻结肩的成纤维细胞增殖和致密胶原基质沉积的病理生理机制尚不清楚。警报素（也称为危险信号）是在感染或组织损伤后释放到细胞外环境中的内源性分子，它们发出细胞和组织损伤的信号。
研究特发性冻结肩患者中警报素的存在是否高于对照组。
对照实验室研究。
从 10 例特发性冻结肩患者和 10 例不稳定肩患者（对照组）的肩关节囊中采集样本。用苏木精和伊红（H&E）染色，并用针对警报素分子（包括高迁移率族蛋白 B1（HMGB1）、白细胞介素 33、S100A8、S100A9 和周围神经标志物 PGP9.5）的免疫组织化学抗体进行分析。以“无”到“强”的方式对免疫反应性进行盲法评分。注意囊内的免疫组织化学分布。在手术前，记录患者自评的疼痛频率、严重程度、僵硬程度和被动肩部运动范围，并进行统计学分析。
与对照组患者相比，冻结肩患者的自我报告疼痛频率和严重程度更高（P =.02），所有平面的运动范围受限更严重（P <.05）。H&E 染色的冻结肩囊组织显示成纤维细胞增生和滑膜下血管增多。与对照组囊相比，冻结肩囊的警报素免疫反应性明显更强（P <.05）。此外，警报素分子 HMGB1 的表达与患者报告的疼痛严重程度显著相关（r > 0.9，P <.05）。
本研究表明关键分子危险信号在冻结肩中可能起作用，并提示危险分子的表达与患者的疼痛有关。
