Widespread Vascularization and Correlation of Glycosaminoglycan Accumulation to Tendon Pain in Human Plantar Fascia Tendinopathy

Max F.R. Merkel, Rene B. Svensson, Jens R. Jakobsen, Abigail L. Mackey, Peter Schjerling, Robert B. Herzog, S. Peter Magnusson, Lars Konradsen, Michael R. Krogsgaard, Michael Kjær, Finn E. Johannsen
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Abstract

Background:Plantar fasciitis is a painful tendinous condition (tendinopathy) with a high prevalence in athletes. While a healthy tendon has limited blood flow, ultrasound has indicated elevated blood flow in tendinopathy, but it is unknown if this is related to a de facto increase in the tendon vasculature. Likewise, an accumulation of glycosaminoglycans (GAGs) is observed in tendinopathy, but its relationship to clinical pain is unknown.Purpose:To explore to what extent vascularization, inflammation, and fat infiltration were present in patients with plantar fasciitis and if they were related to clinical symptoms.Study Design:Descriptive laboratory study.Methods:Biopsy specimens from tendinopathic plantar fascia tissue were obtained per-operatively from both the primary site of tendon pain and tissue swelling (“proximal”) and a region that appeared macroscopically healthy at 1 to 2 cm away from the primary site (“distal”) in 22 patients. Biopsy specimens were examined with immunofluorescence for markers of blood vessels, tissue cell density, fat infiltration, and macrophage level. In addition, pain during the first step in the morning (registered during an earlier study) was correlated with the content of collagen and GAGs in tissue.Results:High vascularization (and cellularity) was present in both the proximal (0.89%) and the distal (0.96%) plantar fascia samples, whereas inconsistent but not significantly different fat infiltration and macrophage levels were observed. The collagen content was similar in the 2 plantar fascia regions, whereas the GAG content was higher in the proximal region (3.2% in proximal and 2.8% in distal; P = .027). The GAG content in the proximal region was positively correlated with the subjective morning pain score in the patients with tendinopathy (n = 17).Conclusion:In patients with plantar fasciitis, marked tissue vascularization was present in both the painful focal region and a neighboring nonsymptomatic area. In contrast, the accumulation of hydrophilic GAGs was greater in the symptomatic region and was positively correlated with increased clinical pain levels in daily life.Clinical Relevance:The accumulation of GAGs in tissue rather than the extent of vascularization appears to be linked with the clinical degree of pain symptoms of the disease.
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人类足底筋膜肌腱病的广泛血管化和糖胺聚糖积累与肌腱疼痛的相关性
背景:足底筋膜炎是一种疼痛性肌腱疾病(肌腱病),在运动员中发病率很高。虽然健康肌腱的血流量有限,但超声波显示肌腱病的血流量升高,但不知道这是否与肌腱血管事实上的增加有关。目的:探讨足底筋膜炎患者的血管化、炎症和脂肪浸润程度,以及它们是否与临床症状有关。研究设计:描述性实验室研究。方法:22 例患者的腱病性足底筋膜炎组织活检标本均在手术前从肌腱疼痛和组织肿胀的主要部位("近端")和距主要部位 1 到 2 厘米处("远端")的宏观健康区域获得。活检标本采用免疫荧光法检测血管、组织细胞密度、脂肪浸润和巨噬细胞水平等标记物。结果:近端(0.89%)和远端(0.96%)的足底筋膜样本均存在高血管化(和细胞化),而脂肪浸润和巨噬细胞水平不一致,但无显著差异。两个足底筋膜区域的胶原蛋白含量相似,而近端区域的 GAG 含量更高(近端为 3.2%,远端为 2.8%;P = 0.027)。结论:在足底筋膜炎患者中,疼痛灶区域和邻近的无症状区域都存在明显的组织血管化。临床意义:组织中 GAGs 的积累而非血管化程度似乎与该疾病的临床疼痛症状程度有关。
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