Department of Anesthesia, Pain and Palliative Care, Federal University of Maranhão, Maranhão, Brazil.
Experimental Laboratory for the Study of Pain, Federal University of Maranhão, Maranhão, Brazil.
PLoS One. 2021 Jan 12;16(1):e0245194. doi: 10.1371/journal.pone.0245194. eCollection 2021.
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.
由于使用的药物疗效低,骨关节炎的药物治疗仍然不足。关节内(i.a.)给予右美托咪定可能是治疗骨关节炎相关疼痛的一种选择。本研究评估了不同剂量右美托咪定通过 i.a.途径在实验性大鼠膝骨关节炎模型中的镇痛和抗炎作用,该模型通过 i.a.途径注射单碘乙酸(MIA)诱导。将大鼠分为 4 组,每组 24 只。OA(骨关节炎)、DEX-1(右美托咪定 1μg/kg)和 DEX-3(右美托咪定 3μg/kg)组通过 i.a.途径向右侧膝关节注射单碘乙酸(MIA)诱导骨关节炎;对照组未诱导骨关节炎。在第 0 天(骨关节炎诱导前)和诱导后第 5、10、14、21 和 28 天进行临床评估。第 7 天通过 i.a.途径给药,剂量为 1 和 3μg/kg,同时 OA 组给予 0.9%生理盐水。在第 7、14、21 和 28 天处死动物。收集滑膜组织样本进行组织病理学分析,并收集腘窝淋巴结测量细胞因子(白细胞介素[IL]IL-6、肿瘤坏死因子α[TNF-α])。右美托咪定(1 和 3μg/kg)在骨关节炎慢性退行性阶段显著减少了动物的体重分布缺陷,并在整个实验过程中提高了疼痛阈值。组织学分析表明,右美托咪定对滑膜没有造成任何额外的损伤。与 OA 组相比,DEX-3 组在第 28 天 TNF-α水平显著降低。右美托咪定通过临床参数减轻了大鼠骨关节炎的疼痛,但对组织学评估没有抗炎作用。