Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Arthritis Res Ther. 2010;12(2):R41. doi: 10.1186/ar2950. Epub 2010 Mar 11.
Pristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed.
Arthritis was induced in DA.rats by injection of 150 microl 2,6,10,4-tetramethyl-pentadecane (pristane) at the base of the tail and changes in locomotor behaviour of the affected paws were monitored using the CatWalk quantitative gait analysis system. The pathologic events occurring in the joints of pristane-injected animals were studied before onset, at onset, and during acute phase of arthritis by histological methods.
Gait analysis revealed that changes in locomotion such as reduced paw print areas and stance phase time are already apparent before the onset of clinically discernible arthritis symptoms (erythema, paw swelling) and correlate with PIA scores. In agreement with these findings, inflammatory tenosynovitis could be observed by histology already before the onset of erythema and swelling of the respective paws. In the most heavily affected rats also irregularities in step sequence patterns occurred A kinetic analysis of clinical and histological findings demonstrated that gait changes precede the pathological changes occurring during the acute phase of pristane-induced arthritis.
Gait analysis allows for pinpointing the initial inflammatory changes in experimental arthritis models such as pristane-induced arthritis. Analysis of early clinically relevant symptoms in arthritis models may facilitate the search for novel therapeutics to interfere with pain, inflammation and joint destruction in patients suffering from inflammatory arthritis.
已将大鼠中的油诱导关节炎(PIA)描述为一种具有类似人类类风湿关节炎特征的炎症性关节炎动物模型,例如外周关节的慢性、破坏性和对称性受累。然而,到目前为止,人们对最早的炎症事件及其对 PIA 过程中运动行为的影响知之甚少。为了研究这个问题,对 PIA 的前驱期和早期发生的病理变化进行了详细分析。
通过在尾巴底部注射 150 微升 2,6,10,4-四甲基十五烷(油)在 DA.rats 中诱导关节炎,并使用 CatWalk 定量步态分析系统监测受影响爪子的运动行为变化。通过组织学方法研究了注射油的动物关节中发生的病理事件,在关节炎发作前、发作时和急性发作时。
步态分析表明,运动变化,如减少的足印面积和站立时间,在可临床识别的关节炎症状(红斑、爪子肿胀)出现之前就已经明显,并且与 PIA 评分相关。与这些发现一致,在红斑和肿胀出现之前,通过组织学已经可以观察到炎症性腱鞘炎。在受影响最严重的大鼠中,步幅序列模式也出现不规则。对临床和组织学发现的动力学分析表明,步态变化先于油诱导关节炎急性发作期间发生的病理变化。
步态分析可精确定位实验性关节炎模型(如油诱导关节炎)中的初始炎症变化。对关节炎模型中早期临床相关症状的分析可能有助于寻找新的治疗方法来干扰患有炎症性关节炎的患者的疼痛、炎症和关节破坏。