Katole Nilesh T, Kale Jyoti S, Salankar Harsh V
Pharmacology and Therapeutics, Datta Meghe Medical College, Datta Meghe Institute of Medical Sciences, Nagpur, IND.
Physiology, Datta Meghe Medical College, Datta Meghe Institute of Medical Sciences, Nagpur, IND.
Cureus. 2022 Jul 16;14(7):e26910. doi: 10.7759/cureus.26910. eCollection 2022 Jul.
Statins are well-established agents for dyslipidemia and have successfully been used for the prevention of coronary artery diseases for a long time; this is attributed not only to their lipid-lowering action but also to their pleiotropic actions. Recently many pleiotropic actions of statins have been explored, but very few studies were done to explore statins' antinociceptive action; therefore, the current study was planned to evaluate the antinociceptive activity of Simvastatin in different pain models in mice.
Antinociceptive activity of Simvastatin was evaluated by using Eddy's hot plate method (central analgesic model), acetic acid-induced writhing method (peripheral analgesic model), and biphasic formalin-induced paw licking method. Twenty-four mice were divided into four groups (n = 6 in each): Vehicle control group, simvastatin 5mg/kg, simvastatin 20mg/kg, and positive control group.
In the hot plate method, as compared to the vehicle control group, Simvastatin 20mg/kg group showed a significant rise in the reaction time to the corresponding time interval (p<0.001). While the simvastatin 5mg/kg group did not show any significant analgesic activity in the hot plate test. In the acetic acid writhing method, both test groups show a significant delay in the onset of writhing and a decrease in the number of writhes as compared to the vehicle control group (P<0.001). While in the formalin test, both groups show dose-dependent analgesic activity in both the early and late phases.
Simvastatin exhibits analgesic activity in both central as well as peripheral models of analgesia, but central analgesia shows only at higher concentrations. Similarly, it inhibits inflammatory pain more predominantly than neurogenic, and hence simvastatin can be used in inflammatory conditions like rheumatoid arthritis and osteoarthritis particularly when there is coexisting dyslipidemia.
他汀类药物是治疗血脂异常的常用药物,长期以来成功用于预防冠状动脉疾病;这不仅归因于其降脂作用,还归因于其多效性作用。最近,人们对他汀类药物的许多多效性作用进行了探索,但很少有研究探讨他汀类药物的抗伤害感受作用;因此,本研究旨在评估辛伐他汀在小鼠不同疼痛模型中的抗伤害感受活性。
采用Eddy热板法(中枢镇痛模型)、醋酸诱导扭体法(外周镇痛模型)和双相福尔马林诱导舔足法评估辛伐他汀的抗伤害感受活性。将24只小鼠分为四组(每组n = 6):溶剂对照组、辛伐他汀5mg/kg组、辛伐他汀20mg/kg组和阳性对照组。
在热板法中,与溶剂对照组相比,辛伐他汀20mg/kg组在相应时间间隔的反应时间显著延长(p<0.001)。而辛伐他汀5mg/kg组在热板试验中未显示出任何显著的镇痛活性。在醋酸扭体法中,与溶剂对照组相比,两个试验组的扭体发作均显著延迟,扭体次数减少(P<0.001)。而在福尔马林试验中,两组在早期和晚期均显示出剂量依赖性镇痛活性。
辛伐他汀在中枢和外周镇痛模型中均表现出镇痛活性,但中枢镇痛仅在较高浓度时出现。同样,它对炎性疼痛的抑制作用比神经源性疼痛更显著,因此辛伐他汀可用于类风湿性关节炎和骨关节炎等炎性疾病,特别是在存在血脂异常的情况下。