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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin
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Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin

机译：辛伐他汀的联合给药对吗啡镇痛耐受性和身体依赖性的调节

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Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, are widely used in the management of different diseases beyond their primary indication for lowering cholesterol. Previous studies have demonstrated the neuroprotective effects of simvastatin in different animal models. In the present study, we examined the effects of simvastatin (30, 60, 100 and 300 mg/kg, p.o.) on the development and expression of morphine-induced tolerance and dependence in mice. For the induction of morphine tolerance and dependence, mice were twice daily treated with morphine (10 mg/kg, s.c.) for 5 consecutive days. Tolerance was evaluated by the hot-plate test and physical dependence by naloxone challenge, on the sixth day. The results showed that oral administration of simvastatin produced antinociceptive activity in a dose-dependent way. Co-administration of simvastatin with morphine did not affect the acute morphine-induced analgesia (10 mg/kg, s.c.). However, repeated co-administration of simvastatin with morphine significantly attenuated the development of tolerance to the analgesic effect of morphine and inhibited the naloxone (5 mg/kg, s.c.)-precipitated withdrawal signs (jumping and body weight loss). Also, simvastatin at doses of 100 and 300 mg/kg attenuated the expression of morphine-induced tolerance and dependence. These data indicated that, while simvastatin can alleviate both development and expression of morphine-induced tolerance, it cannot enhance morphine-induced antinociception. Taken together, simvastatin may be used as an adjutant therapeutic agent in combination with morphine and or other opioids in patients with severe chronic pain. (C) 2015 Elsevier Inc All rights reserved.
机译：他汀类药物（3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂）已广泛用于各种疾病的管理，而不仅仅是降低胆固醇的主要适应症。先前的研究表明辛伐他汀在不同动物模型中的神经保护作用。在本研究中，我们检查了辛伐他汀（30、60、100和300 mg / kg，p.o.）对吗啡诱导的小鼠耐受性和依赖性的发展和表达的影响。为了诱导吗啡耐受性和依赖性，每天两次用吗啡（10mg / kg，皮下注射）连续5天对小鼠进行处理。在第六天，通过热板测试评估耐受性，并通过纳洛酮挑战评估身体依赖性。结果表明，辛伐他汀口服给药具有剂量依赖性的抗伤害感受活性。辛伐他汀与吗啡并用不会影响急性吗啡引起的镇痛作用（10 mg / kg，皮下注射）。然而，辛伐他汀与吗啡的反复共同给药显着减弱了对吗啡镇痛作用的耐受性，并抑制了纳洛酮（5 mg / kg，皮下注射）沉淀的戒断症状（跳跃和体重减轻）。同样，辛伐他汀在100和300 mg / kg的剂量下也会减弱吗啡诱导的耐受性和依赖性的表达。这些数据表明，尽管辛伐他汀可以减轻吗啡诱导的耐受性的发展和表达，但不能增强吗啡诱导的抗伤害感受。总之，辛伐他汀可以与吗啡和/或其他阿片类药物联合用作重度慢性疼痛患者的辅助治疗剂。 （C）2015 Elsevier Inc保留所有权利。

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