Comprehensive catwalk gait analysis in a chronic model of multiple sclerosis subjected to treadmill exercise training

Multiple sclerosis (MS) is a demyelinating disease with a wide range of symptoms including walking impairment and neuropathic pain mainly represented by mechanical allodynia. Noteworthy, exercise preconditioning may affect both walking impairment and mechanical allodynia. Most of MS symptoms can be reproduced in the animal model named experimental autoimmune encephalomyelitis (EAE). Usually, neurological deficits of EAE are recorded using a clinical scale based on the development of disease severity that characterizes tail and limb paralysis. Following paralysis recovery, subtle motor alterations and even mechanical allodynia investigation are difficult to record, representing sequels of peak disease. The aim of the present study was to investigate the walking dysfunction by the catwalk system (CT) in exercised and non-exercised C57BL/6 mice submitted to EAE with MOG_35-55 up to 42 days post-induction (dpi).

Twenty-four C57BL/6 female mice were randomly assigned to unexercised (n = 12) or exercised (n = 12) groups. The MOG_35-55 induced EAE model has been performed at the beginning of the fifth week of the physical exercise training protocol. In order to characterize the gait parameters, we used the CT system software version XT 10.1 (Noldus Inc., The Netherlands) from a basal time point (before induction) to 42 days post induction (dpi). Statistical analyses were performed with GraphPad Prisma 4.0 software.

Data show dynamic gait changes in EAE mice including differential front (FP) and hind paw (HP) contact latency. Such findings are hypothesized as related to an attempt to maintain balance and posture similar to what has been observed in patients with MS. Importantly, pre-exercised mice show differences in the mentioned gait compensation, particularly at the propulsion sub-phase of HP stand. Besides, we observed reduced intensity of the paw prints as well as reduced print area in EAE subjects, suggestive of a development of chronic mechanical allodynia in spite of being previously exercised.

Our data suggest that Catwalk system is a useful tool to investigate subtle motor impairment and mechanical allodynia at chronic time points of the EAE model, improving the functional investigation of gait abnormalities and demyelination sequelae.