Effect of intra-articular dexmedetomidine on experimental osteoarthritis in rats

Abstract

Pharmacological treatment of osteoarthritis is still inadequate due to the low efficacy of the drugs used. Dexmedetomidine via the intra-articular (i.a.) route might be an option for the treatment of osteoarthritis-associated pain. The present study assessed the analgesic and anti-inflammatory effects of dexmedetomidine administered via the i.a. route in different doses in an experimental model of rat knee osteoarthritis induced with monosodium iodoacetate. Rats were allocated to four groups with 24 animals in each group. The OA (osteoarthritis), DEX-1 (dexmedetomidine in dose of 1μg/kg) and DEX-3 (dexmedetomidine in dose of 3μg/kg) groups were subjected to induction of osteoarthritis through injection of monosodium iodoacetate (MIA) via the i.a. route on the right knee; the control group was not subjected to osteoarthritis induction. Clinical assessment was performed on day 0 (before osteoarthritis induction) and then on days 5, 10, 14, 21 and 28 after induction. Treatment was performed on day 7 via the i.a. route, consisting of dexmedetomidine in doses of 1 and 3 μg/kg, while group OA received 0.9% normal saline. The animals were euthanized on days 7, 14, 21 and 28. Samples of the synovial membrane were collected for histopathological analysis, and the popliteal lymph nodes were collected for measurement of cytokines (interleukin [IL] IL-6, tumor necrosis factor alpha [TNF-α]). Dexmedetomidine (1 and 3 μg/kg) significantly reduced the animals' weight distribution deficit during the chronic-degenerative stage of osteoarthritis and improved the pain threshold throughout the entire experiment. Histological analysis showed that dexmedetomidine did not cause any additional damage to the synovial membrane. The TNF-α levels decreased significantly in the DEX-3 group on day 28 compared with the OA group. Dexmedetomidine reduced pain, as evidenced by clinical parameters of osteoarthritis in rats, but did not have an anti-inflammatory effect on histological evaluation.

Fig 1. Flowchart representing the experimental protocol.

Fig 2. Assessment of weight distribution on the hind paws in rats treated with normal saline (0.9% NaCl, i.a.) or dexmedetomidine at doses of 1 μg/kg or 3 μg/kg, i.a.

Symbols and vertical lines represent the mean ± standard error of the mean. The vertical dotted lines represent the onset of treatment. * indicates a significant difference compared with the control group. # indicates a significant difference compared with the OA group.

Fig 3. Assessment of tactile allodynia in rats treated with normal saline (0.9% NaCl, i.a.) or dexmedetomidine (1 μg/kg or 3 μg/kg, i.a.).

Symbols and vertical lines represent the mean ± standard error of the mean. The vertical dotted line represents the onset of treatment. * indicates a significant difference compared with the control group. # indicates a significant difference compared with the OA group. + indicates a significant difference compared with the DEX 3 μg/kg group.

Fig 4. Histopathological analysis of the synovial membrane.

A) Edema and moderate chronic lymphoplasmacytic inflammatory infiltrate with formation of lymphoid follicle and synovial hyperplasia. B) Edema and moderate chronic lymphoplasmacytic inflammatory infiltrate with focal areas of fibrosis. C) Inflammatory infiltrate with intense fibrosis of the synovial membrane.