In the collagen-induced arthritis (CIA) mouse model, inflammation readouts are usually quantified using operator-dependent clinical scoring systems, and no systematic relationship with functional deficits has been detected. In this study, we extensively quantified sensory and motor deficits in CIA mice during natural disease progression and therapeutic treatment. Then, we used these data to build a scale to predict functional deficits on the basis of the classical clinical score. Using the CIA mouse model, we longitudinally screened multiple approaches to assess locomotion (open field test, Catwalk™), sensitivity (Von Frey, Hargreaves, static weight-bearing tests), and inflammation (skin temperature), and identified the most accurate tests to correlate sensory and motor deficits with disease severity, measured by clinical score. We then used these tests to characterize functional deficits in control (naïve and mice injected with complete Freund’s adjuvant) and CIA mice, either untreated or treated with methotrexate to prevent functional deficits. By mathematical approaches, we finally investigated the relationship between functional deficits and clinical score. We found that the functional disability scores obtained with the open field, Catwalk™, Hargreaves, and skin temperature tests significantly correlated with the clinical score in CIA mice, either untreated or treated with methotrexate. Mathematical correlation showed that motor deficits, robustly characterized by two different tests, were twice more responsive than thermal sensitivity deficits. We propose the arthritis sensory and motor (ArthriSM) scale as a new theranostic tool to predict motor and sensory deficit based on the clinical score, in the experimental mouse model of CIA. This ArthriSM scale may facilitate the transfer of knowledge between preclinical and clinical studies.

中文翻译：

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关节炎的感觉和运动量表：根据胶原诱导的关节炎的临床评分预测功能障碍。

在胶原诱导的关节炎（CIA）小鼠模型中，通常使用依赖于操作员的临床评分系统来量化炎症读数，并且未检测到与功能缺陷的系统关系。在这项研究中，我们广泛地量化了CIA小鼠在自然疾病进展和治疗过程中的感觉和运动缺陷。然后，我们使用这些数据建立了一个在经典临床评分基础上预测功能缺陷的量表。使用CIA小鼠模型，我们纵向筛选了多种方法来评估运动（露天测试，Catwalk™），敏感性（冯·弗雷，哈格里夫斯，静态负重测试）和炎症（皮肤温度），并确定了最准确的测试通过临床评分将感觉和运动功能障碍与疾病严重程度相关联。然后，我们使用这些测试来表征对照组（未治疗的小鼠和注射了完全弗氏佐剂的小鼠）和CIA小鼠的功能缺陷，这些小鼠未经治疗或用甲氨蝶呤治疗以预防功能缺陷。通过数学方法，我们最终研究了功能缺陷与临床评分之间的关​​系。我们发现，在未经治疗或未经甲氨蝶呤治疗的CIA小鼠中，通过开放视野，Catwalk™，Hargreaves和皮肤温度测试获得的功能障碍评分与CIA临床评分显着相关。数学相关性表明，通过两个不同的测试强有力地表征了运动缺陷，其响应性比热敏感性缺陷高出两倍。我们建议在CIA实验小鼠模型中，将关节炎感觉和运动（ArthriSM）量表作为一种新的治疗方法，根据临床评分预测运动和感觉不足。这种ArthriSM量表可以促进临床前研究与临床研究之间的知识转移。