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.
Highlights
Osteoarthritis (OA) is a degenerative disease characterized by progressive degeneration of the knee cartilage accompanied by secondary inflammation of the synovial membrane
On day 1, OA was induced in groups B, C and D using monosodium iodoacetate (MIA)
In the animals with OA, the changes induced by MIA followed a biphasic distribution
Summary
Osteoarthritis (OA) is a degenerative disease characterized by progressive degeneration of the knee cartilage accompanied by secondary inflammation of the synovial membrane. This disease is defined as a heterogeneous group of conditions that cause painful joint signs and symptoms associated with defects of joint cartilage integrity [1]. Clonidine [3], fadolmidine [4] and dexmedetomidine [5,6] have been studied to improve the current understanding of their local and systemic analgesic effects, so that they might be better used for treatment of diseases involving inflammation and pain, such as OA
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