Faculty of Medicine, The University of Jordan, Amman, 11942, Jordan.
Faculty of Pharmacy, Philadelphia University, Amman, Jordan.
Inflammopharmacology. 2019 Dec;27(6):1131-1142. doi: 10.1007/s10787-019-00584-7. Epub 2019 Apr 3.
Osteoarthritis (OA) is characterized by cartilage degeneration, subchondral sclerosis, and pain. Cannabinoids have well-established anti-nociceptive properties in animal models of chronic pain. The aim of this study is to evaluate the anti-nociceptive effects of synthetic cannabinoids (WIN-55,212 and HU210) and the cannabinoid-like compound palmitoylethanolamide (PEA) in rat models of OA and to assess the role of cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor α (PPARα) in mediating these effects. Intra-articular injection of monosodium iodoacetate (MIA) in the knee joint was used as a model of osteoarthritis. The von Frey filament test and weight-bearing difference were used to assess the anti-nociceptive effects of WIN-55,212, HU210, and PEA on MIA-induced OA in rats. Open-field locomotor activity system was used confirm the analgesic effects of those compounds. HU210, WIN55, 212, and PEA in a dose-dependent manner restored the paw withdrawal threshold (PWT) and the weight-bearing difference induced by MIA injection. SR141716A (a CB1 antagonist) significantly reversed the anti-nociceptive effects of all the administered drugs in terms of PWT. However, in terms of weight-bearing difference, SR141716A significantly reduced the anti-nociceptive effect of HU210 but not PEA or WIN55, 212. GW6471 (a PPARα antagonist) significantly reversed the anti-nociceptive effects of PEA but not those of HU210 or WIN55, 212. HU210, WIN55, 212 and PEA significantly restored the MIA-induced reduction in locomotor activity. In conclusions, both CB1 and PPARα receptors are involved in mediating pain in osteoarthritis. Therefore, targeting these receptors may be of great clinical value.
骨关节炎（OA）的特征为软骨退化、软骨下骨硬化和疼痛。大麻素在慢性疼痛的动物模型中具有明确的抗伤害感受特性。本研究的目的是评估合成大麻素（WIN-55,212 和 HU210）和大麻素类似物棕榈酸乙醇酰胺（PEA）在 OA 大鼠模型中的抗伤害感受作用，并评估大麻素受体 1（CB1）和过氧化物酶体增殖物激活受体α（PPARα）在介导这些作用中的作用。膝关节注射单碘乙酸盐（MIA）被用作骨关节炎模型。von Frey 细丝试验和体重差异用于评估 WIN-55,212、HU210 和 PEA 对 MIA 诱导的 OA 大鼠的抗伤害感受作用。开放式运动活动系统用于证实这些化合物的镇痛作用。HU210、WIN55,212 和 PEA 以剂量依赖的方式恢复了 MIA 注射引起的爪回缩阈值（PWT）和体重差异。SR141716A（CB1 拮抗剂）显著逆转了所有给予药物在 PWT 方面的抗伤害感受作用。然而，在体重差异方面，SR141716A 显著降低了 HU210 的抗伤害感受作用，但不降低 PEA 或 WIN55,212 的抗伤害感受作用。GW6471（PPARα 拮抗剂）显著逆转了 PEA 的抗伤害感受作用，但不逆转 HU210 或 WIN55,212 的抗伤害感受作用。HU210、WIN55,212 和 PEA 显著恢复了 MIA 诱导的运动活动减少。总之，CB1 和 PPARα 受体都参与介导骨关节炎疼痛。因此，针对这些受体可能具有重要的临床价值。
