The adjuvant-induced rat model of monoarthritis: welfare implications and possible refinement strategies

Abstract

This study investigated welfare, mechanical hyperalgesia and model specific parameters (mobility, stance, joint stiffness and ambulation impairment) during a three-week period in a rat model of monoarthritis. The objective was to identify possible targets for refinement of the model and consequently improve animal welfare. Monoarthritis was induced in eight male Sprague-Dawley rats by an intra-articular injection of 20 µL Complete Freund’s Adjuvant (CFA containing heat-killed Mycobacterium tuberculosis) in the left tibio-tarsal joint. The effects on subjects were monitored daily and compared to a negative control group. The induced monoarthritic response consisted of pronounced acute inflammation observed as joint swelling, redness and temperature rise in the injected hind leg. Several parameters such as bodyweight, mobility, stance, stiffness and ambulation were also affected. All CFA-injected rats demonstrated a significantly higher nociceptive response in an electronic von Frey test throughout the study, with a markedly lower mechanical threshold in the first three days after injection. Complete Freund’s Adjuvant was sufficient to induce monoarthritis in all CFA-injected rats. It is concluded that more attention should be paid to alleviating pain in the acute phase where the animal’s well-being appears to be most compromised, and that an injection volume of 20 µL CFA is sufficient to induce monoarthritis in the tibio-tarsal joint.