Refining the adjuvant-induced rat model of monoarthritis by optimizing the induction volume and injection site

Arthritis is a highly prevalent and disabling condition characterized by pathological joint-damage, clinical symptoms of pain and loss of normal joint function. Monoarthritis can be modelled in rodents via intraarticular injection of complete Freund's Adjuvant (CFA), inducing both joint inflammation and pain-like behaviours. This study aimed to compare the outcome of different injection-volumes and joint-locations, to refine the model's use and to improve its validity. Male and female rats were injected with CFA into the ankle (10, 20 or 50 µl) or knee (10, 50 or 100 µl), and assessed on dynamic weight bearing, locomotor activity, depressive- and anxiety-like behaviours, histology, and a variety of welfare and model-specific parameters. Induction of monoarthritis resulted in relatively similar behavioural profiles regardless of the injected joint. The animals were highly affected in the acute phase, while less in the chronic phase. Greater volumes of CFA were associated with more profound behavioural changes and joint swelling. The largest volumes induced a pronounced local spread of inflammation to adjacent joints, which was reduced with intermediate volumes without attenuating the model validity. Reducing induction volumes to 20 and 50 µl CFA for ankle and knee injections, respectively, appears to be valuable refinement of these models.Competing Interest StatementKSPA received funding for the project: 33010-NIFA-14-586, from the Danish 3R Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript