Association between arthritis score at the onset of the disease and long-term locomotor outcome in adjuvant-induced arthritis in rats

Abstract

Introduction: To investigate the connection between the intensity of initial symptoms of inflammation and locomotor outcome in rheumatoid arthritis, we examined the relationship between long-term locomotor abnormalities and signs of inflammation at the onset of the disease in adjuvant-induced arthritis (AIA) in rats. Methods: The arthritis score and hind-paw diameter were followed from immunization to day 195 (~7 months). At this time, locomotion was recorded during forced treadmill walking using 3D motion technology before radiographic scoring of hind limb joint damage. Many locomotor parameters were analyzed including time and length parameters, limbs kinematics, lateral paw position at toe off, maximal hind-paw elevation and posture. Ankle mobility was assessed from range of motion (ROM) of the joint during locomotion. Experiments were run in AIA (n = 18) and age-matched non-AIA rats (n = 8). Results: All AIA rats exhibited signs of inflammation at day 14 with a peak of inflammatory symptoms at day 22 post-immunization. After the first episode of inflammation, 83 % of AIA rats demonstrated recurrent disease (from week 6 to week 23). The frequency of inflammatory episodes (1 to 5) was not linked to the arthritis score at day 22. At day 195 post-immunization, AIA rats showed significantly impaired locomotion and radiographic lesions as compared to control rats. Significant relationships were observed between most locomotion-related parameters and concurrent ROM of ankle, which correlated negatively with the radiographic score. ROM of ankle at day 195 correlated negatively with both the arthritis score and hind-paw diameter measured at day 14, 22 and 30 post-immunization. Conclusion: Decreased ankle mobility can be considered a driver of locomotion impairment in AIA. In this model, the severity of the initial inflammatory symptoms had a good prognostic value for long-term locomotor outcome.