The results of this study show that CFA-induced monoarthritis in C57BL/6 mice results in changes in static and dynamic gait parameters which can be quantified by the CatWalk system. These changes are not due to the effects of the injection process or volume of liquid because intra-articular administration of PBS did not affect any of the mice gait parameters. The extent of alleviation of the CFA-induced monoarthritis deficits in gait parameters by treatment with a non-steroidal anti-inflammatory drug, indomethacin, can also be quantified using the CatWalk system.
Using a systematic literature search within the PubMed database we found nine studies that have used the CatWalk system to study rodent models of arthritis [8–16]. However, almost all of these studies (seven out of nine) have been dedicated to the study of rat models of arthritis [9–14, 16]. The two studies that used mice used the C57BL/6 mice, inoculated with LPS into the RH limb, evaluated principally static parameters i.e. paw pressure and print area [8, 15]. However, other gait analysis systems such as the DigiGait Imaging System (Mouse Specifics, Inc.), have been used to evaluate both static and dynamic parameters in mice with CIA .
Complete Freund’s adjuvant has been used extensively to induce arthritis in rodents including mice [21–23]. Using an observer based-rating scale, mice with CFA-induced monathritis have been reported to have impaired stance and gait . Recently, a study using rats showed that CFA-induced monoarthritis resulted in deficits in load/weight bearing in the ipslateral limb . In the current study, using the automated CatWalk system, reduced weight bearing on the ipslateral limb in mice with CFA-induced monoarthritis was also recorded, which resulted in a reduced weight bearing ratio of the ipslateral to the contralateral hind limb. Akin to the LPS-induced monoarthritis mouse model , reduced paw print area was observed in the ipslateral limb of mice with CFA-induced monoarthritis. These deficits were alleviated by treatment with indomethacin, comparable to what was previously observed in the LPS-induced monoarthritis mouse model . These observations resemble the clinical situation in patients taking into consideration that in patients with unilateral knee osteoarthritis pain relief in the affected knee resulted in even load distribution between the legs .
Besides weight bearing, dynamic parameters such as velocity and stride length are altered in human patients with rheumatoid arthritis and these changes correlate closely with lower limb pain . This is the first study where changes in dynamic parameters such as stance phase duration, swing phase duration, duty cycle and swing speed quantified by the CatWalk system have been reported in a mouse model of arthritis. Similar to what has been reported in rat models of arthritis stance phase duration and duty cycle (expressed in these other studies as fraction of total step duration or duty factor) [9, 13] were decreased in the ipslateral limb compared to the contralateral limb in mice with monoarthritis. Treatment with indomethacin alleviated the deficits in stance phase duration and duty cycle in arthritic mice. Analgesics such as morphine and rofecoxib have also been shown to improve changes related to stance phase duration in rats with carrageenan-induced arthritis . Swing phase duration and speed were also changed in mice with arthritis i.e. swing phase duration was increased and swing speed was decreased. These parameters were improved in mice treated with indomethacin. These findings concur with what has been reported in rats with monoiodoacetate-induced arthritis both in terms of deficits and improvement after treatment with an analgesic, celecoxib .