New tool to assess walking patterns in the development of OA pain: kinetic weight bearing

Purpose: Osteoarthritis (OA), or degenerative joint disease, is a debilitating condition associated with pain that remains only partially controlled by available analgesics. Patients living with OA often exhibit abnormal movement patterns primarily due to altered joint kinematics. While some of these gait changes in OA are due to deterioration in joint congruency, compensatory movement to minimize joint loading and pain is also likely to play a part. Monitoring animal movement following arthritis induction could reveal some interesting insights into pain perception. Analyzing knee biomechanics during walking - the primary cyclic load-bearing activity - is therefore particularly relevant. Better understanding the differences in biomechanics between non-OA and OA individuals offers a unique basis to study the disease and improve prevention and treatment options. The current gap between basic science research and new analgesic development presents a serious challenge for the future of pain medicine. Therefore, a paradigm shift in translational pain research is necessary to transform the current strategy and to explain why animal behavioral testing does not assess subjective pain experience. Methods: We employed the OA model for the study of joint pain induced by the injection of monosodium iodoacetate (MIA) into the knee of rats. Behavioral changes resemble some of the symptoms reported by the patient population. Weight bearing deficits have been observed in MIA model. While most studies investigate the weight distribution on the two hind paws measured as the force exerted by each limb on a transducer plate in the floor over a given time period we used Kinetic Weight Bearing (KWB), a novel instrument developed by Bioseb (France) and designed to measure time and spatial distribution of a weight bearing by each paw in freely moving rodent. KWB quantifies over 20 parameters describing spontaneous movement patterns. We aimed at comparison of sensory system evaluation by joint hypersensitivity (Pressure Application Measurement, PAM) and gait analysis (KWB) to define their benefits for the study of OA-related pain and more accurate transition from bench to bedside. Results: PAM measurements showed biphasic development of pain behavior with acute response at day 2 and phase recognized as associated with cartilage degeneration starting at day 10-14 after MIA i.a. injection. KWB measurements presented similar pattern of response, where changes in walking pattern were more pronounced at the beginning and the end of experiment. The most abundant alternations were observed when rear left (RL) and rear right (RR) paws were compared in each of treatment groups, more robust in rats injected with 3mg MIA, rather than in the 1 mg MIA group. Changes in walking pattern were different in acute response to MIA injection and in the developed stages of OA. Changes between groups were pronounced only at the beginning of OA development and around day 21, however no significant differences could be seen. This suggests that dose of 1 mg of MIA used to induce OA is sufficient in the studies on pathophysiology of pain associated with that condition. Conclusions: Hereby we present results on KWB, as an alternative method generating quantitative data on footprints, with the main advantage of allowing to describe subtle changes in locomotor activity of a freely moving animal. Pain behavior measured by this test correlated with well-established PAM assessment, which increase credibility and utility of KWB measurements. Complex description of locomotor activity of rats in MIA model of OA allows to improve accurateness in rating in OA-associated pain. This might be of benefit in assessing effectiveness of novel treatments and better transitioning results from laboratory conditions to clinic. Supported by National Science Centre, Poland grants: OPUS UMO-2014/13/B/NZ7/02311, ETIUDA UMO-2015/16/T/NZ7/00052 and statutory funds.