Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis and bone destruction at the joints, causing pain and motor disturbance. Despite the better control of inflammation and joint deformity afforded by modern disease-modifying anti-rheumatic drugs, many patients with RA remain dissatisfied with their treatment, primarily because of sensory-emotional distress. Pre-clinical tests that can evaluate not only the symptoms of arthritis but also the associated pain as sensory-emotional experience are urgently needed. Here, we introduce two types of novel methods for evaluation of voluntary behavior in a commonly used model of RA (collagen-induced arthritis; CIA) in male mice. First, spontaneous motor activity was assessed with a running wheel placed in home cages and the number of rotations was continuously recorded in a 12:12-h light environment. Second, temperature preference was assessed by measuring the time spent in either of the floor plates with augmenting (25 to 49 °C) or fixed temperature (25 °C). We also evaluated the effects of tofacitinib on CIA-associated changes in voluntary wheel running and temperature preference. We detected a significant decrease in voluntary wheel running, a significant shift in the distribution of movement in the dark phase, and a significant increase in the time spent in warmer environments than the room temperature in the mice with CIA. These alterations in voluntary behavior have never been described with conventional methods. We also revealed tofacitinib-resistant significant changes in the voluntary behavior and choice of temperature despite significant mitigation of the symptoms of arthritis. We described for the first time significant alterations of the voluntary behavior of the mice with CIA during the clinical periods, indicating that the overall physical/motivational states and its circadian variation, as well as the specific preference to a certain environmental temperature, are modified in the mice with CIA, as observed in human patients. Some of these did not parallel with the conventional arthritis scores, particularly during the pharmacotherapy suggesting that mice with CIA show not only the peripheral symptoms but also the central consequences. The use of these approaches would also help clarify the biological mechanisms underlying physician-patient discordance in the assessment of RA.

中文翻译：

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胶原性关节炎小鼠疾病进展和药物治疗过程中自愿行为的改变

类风湿关节炎（RA）是一种自身免疫性疾病，其特征在于慢性滑膜炎和关节的骨质破坏，引起疼痛和运动障碍。尽管现代的能改变疾病的抗风湿药能更好地控制炎症和关节畸形，但许多RA患者仍对治疗不满意，主要是由于感觉情绪困扰。迫切需要临床前测试，不仅可以评估关节炎的症状，还可以评估伴随感觉情感体验的疼痛。在这里，我们介绍两种类型的新颖方法，用于评估雄性小鼠RA（胶原蛋白诱发的关节炎； CIA）的常用模型中的自愿行为。首先，用放置在家庭笼子中的滚轮评估自发运动活动，并以12：1的速度连续记录转数：12小时光照环境。其次，通过测量在增加温度（25到49°C）或固定温度（25°C）的两个地板中所花费的时间来评估温度偏好。我们还评估了托法替尼对CIA相关的自转轮运行和温度偏爱变化的影响。我们检测到自愿轮转的显着减少，在黑暗阶段运动分布的显着变化以及在比CIA小鼠更温暖的环境中花费的时间显着增加。自愿行为的这些变化从未用传统方法描述过。我们还发现尽管明显减轻了关节炎的症状，但对自愿接受的行为和温度选择的耐tofacitinib的显着变化。我们首次描述了在临床期间CIA小鼠的自愿行为的显着变化，表明在正如在人类患者中观察到的那样，具有CIA的小鼠。其中一些与常规关节炎评分不符，特别是在药物治疗期间，这表明CIA小鼠不仅表现出周围症状，而且表现出中心性后果。这些方法的使用还将有助于阐明RA评估中医患矛盾的潜在生物学机制。这表明在患有CIA的小鼠中，正如在人类患者中观察到的那样，整体的身体/动机状态及其昼夜节律的变化以及对特定环境温度的特定偏好发生了变化。其中一些与常规关节炎评分不符，特别是在药物治疗期间，这表明CIA小鼠不仅表现出周围症状，而且表现出中心性后果。这些方法的使用还将有助于阐明RA评估中医患矛盾的潜在生物学机制。这表明在患有CIA的小鼠中，正如在人类患者中观察到的那样，整体的身体/动机状态及其昼夜节律的变化以及对特定环境温度的特定偏好发生了变化。其中一些与常规关节炎评分不符，特别是在药物治疗期间，这表明患有CIA的小鼠不仅表现出周围症状，而且表现出中心性后果。这些方法的使用还将有助于阐明RA评估中医患矛盾的潜在生物学机制。特别是在药物治疗期间，这表明CIA小鼠不仅表现出周围症状，而且还表现出中枢性后果。这些方法的使用还将有助于阐明RA评估中医患矛盾的潜在生物学机制。特别是在药物治疗期间，这表明CIA小鼠不仅表现出周围症状，而且还表现出中枢性后果。这些方法的使用还将有助于阐明RA评估中医患矛盾的潜在生物学机制。