Gait analysis is routinely used in patients with arthritis to assess mobility, prescribe therapy, and monitor rehabilitation. In animal models of arthritis, gait analysis instrumentation such as the DigiGait Imaging System is increasingly being incorporated as a pre-clinical assay for better understanding and treating the arthritic postural and kinematic disturbances.
For example, a recent publication describes the gait of B6 mice with complete Freund’s adjuvant (CFA)-induced arthritis (1). DigiGait, moreover, demonstrated that quantitative postural and kinematic gait metrics correspond to clinical scores with increasing severity in the collagen-induced (CIA) model or rheumatoid arthritis (RA) (2). Likewise, DigiGait quantified gait changes in rats with inflammatory pain following carrageenan injection into the knee joint to model RA (3).
A recent study (1) examined gait in B6 mice injected with CFA (20 ml) intra-articularly into the right ankle joint. Results showed changes in walking patterns and static and dynamic gait parameters.
Video depicts the ventral view of a normal healthy B6 mouse walking on the DigiGait treadmill, with good symmetry of posture and kinematics between the left and right hind limbs. DigiGait provides the opportunity to study multiple strides over a range of speeds.
The authors instead tracked the paw prints of the animals as they made their way across a glass plate, revealing some measurements that were reduced post CFA injection compared to their baseline ratios. These included the ratio of the right hind paw area to the left hind paw area, stance phase duration, duty cycle, and swing speed. Somewhat disingenuously, the authors reported changes in paw pressure. Pressure, however, is a force per unit area that can only be measured via a force transducer. Rather, changes in the intensity of light refracted from the paw being placed on an illuminated glass plate were assumed to reflect changes in pressure. Another shortcoming of the overground paradigm used in the study is the lack of control of walking speed. Walking speed is probably the most important confounder in the interpretation of gait, whether it be humans or rodents; speed affects limb loading, posture, and kinematics. Treatment of the animals with the nonsteroidal anti-inflammatory drug indomethacin (10 mg/kg) alleviated some of the gait disturbances observed. Not known is whether indomethacin increased the walking speed of the animals or how many strides were used in the compilation of the observations.
In the study of CIA mice (2), the DigiGait treadmill paradigm empowered the collection of more data with all animals walking the same speed over numerous strides. CIA mice exhibited increased paw areas, increased stride frequency, shorter stride length, relative paw placement inversion, and reduced stride, stance, braking, swing, and propulsion durations. This study clearly showed that increases in clinical scores that measure the severity of CIA corresponded to changes in multiple gait parameters that reflect both morphologic (increases in paw area) and functional (increase in stride frequency, decrease in stride length, hind-limb paw placement angle, as well as stride, stance, and braking times) deficits. For example, the stance time (the weight-bearing portion of the stride in which the paw remains in contact with the belt) decreased progressively with increasing clinical scores. DigiGait enabled the evaluation and comparison of changes in numerous gait parameters between subjects over numerous strides without the interference of changes in velocity and the requisite changes in gait.
(a) schematic of ventral view of paws as captured by the patented DigiGait ventral plane treadmill videography. From the changes in the areas of the paws the kinematics of the limbs are determined. (b)The gait signals, periodic waveforms representing the advance and retreat of each of four limbs’ motion relative to the treadmill belt.
DigiGait was also employed to characterize the carrageenan monoarthritic rat model, a well-established paradigm of RA and associated pain (3). DigiGait reported significant differences in gait parameters very early after carrageenan injection (4 hours post injection) and long before knee swelling or physical deformities occur. Animals showed the most dramatic changes in temporal and spatial gait parameters in the carrageenan injected right hind limb in response to pain. This study suggests that gait parameters are a suitable and objective method for assessment of early behavioral changes associated with inflammatory pain and may reduce the need for classic indices of hyperalgesia and allodinya.
Ventral view of monoarthritic rat, with indication of which gait metrics were changed 4 hours post intraarticular injection of carrageenan in the right knee.
DigiGait enables the study of animals walking voluntarily, and on a treadmill. The voluntary mode implies that there will be differences in the walking speed between animals and between groups. In our experience, injured animals, animals in pain, and mice with disease may not walk voluntarily, or will walk more slowly and/or with fewer strides than their healthy counterparts. This mandates careful reporting and normalization of the gait parameters because of the well-established effect of speed on gait. The treadmill mode of DigiGait empowers the collection of large amounts of data in all animals at known and equal speeds. This provides lower standard errors and great statistical power in the reported data.
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