Monosodium iodoacetate-induced monoarthritis develops differently in knee versus ankle joint in rats

Objective

Disability and movement-related pain are major symptoms of joint disease, motivating the development of methods to quantify motor behaviour in rodent joint pain models. We compared effects on behaviour, assessed the levels of biochemical mediators and made a detailed histopathological evaluation after induction of rat monoiodoacetate (MIA) monoarthritis into the ankle or knee joint.

Design

Twenty-seven male Lewis rats were used. Before and up to 28 days after induction, they were tested for weight bearing during walking (dynamic), and standing (static), and for mechanical sensitivity. At termination synovial fluid was taken from ankle and/or knee joints for analysis of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), macrophage inflammatory protein 3 alpha (MIP-3α), keratinocyte chemoattractant (KC)/human growth-regulated oncogene (GRO) and L(+)-lactate, and from separate rats joints were collected for histopathological assessment.

Results

MIA ankle joint injection gave a marked reduction of dynamic weight bearing during the first days, not seen in rats with knee joint injection. At three weeks, it was decreased in the group with knee injection, but not in those with ankle injection. However, the different injection sites caused similar reductions in static weight bearing during the early phase, which was normalized in the group with ankle injection but continued and was strengthened with time in the knee injected group. Histopathological assessment, biochemical mediators and joint swelling confirmed the disparate profiles.

Conclusions

This work shows that ankle versus knee joint injection of MIA resulted in different profiles in rats, which may mirror what has been found in human patients with osteoarthritis.