Antinociception induced by rosuvastatin in mice: Modulation by opioid receptor antagonists, risperidone and l-name

Juan Carlos Prieto, Viviana Noriega, Hugo F. Miranda
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Abstract

Statins are widely used in cardiovascular disease as cholesterol lowering drugs. However, they also have other actions (pleiotropic effects) including antiproliferative, antithrombotic, neuroprotective, immunomodulatory, anti-inflammatory and antinociceptive activity. The aim of this study was to determine the antinociception properties of rosuvastatin in two murine models of pain and the involvement of opioid antagonists (naltrexone, naltrindole, norbinaltorphimine), risperidone, and L-NAME (L-NG-nitro arginine methyl ester) in this effect. Rosuvastatin was chosen among available statins because it is commonly prescribed and has high potency, efficacy, and an acceptable safety profile. Rosuvastatin antinociception was evaluated in the acetic acid writhing test and the formalin hind paw test by dose-response curves, before and after the i.p. administration of opioid antagonists, risperidone, and L-NAME. This work demonstrates that the assayed drugs modulate the antinociceptive effect of rosuvastatin in both experimental murine pain tests. The antinociception effect described for rosuvastatin may be due to a particular modulation induced by the opioid antagonists, risperidone and L-NAME. Given the broad effects of rosuvastatin, the results of this study may have novel clinical implications in the therapy of pain.
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洛伐他汀在小鼠体内诱导的抗痛觉作用:阿片受体拮抗剂、利培酮和l-名的调节作用
他汀类药物作为降低胆固醇的药物被广泛用于治疗心血管疾病。然而,他汀类药物还具有其他作用(多效作用),包括抗增殖、抗血栓、神经保护、免疫调节、抗炎和抗痛觉活性。本研究旨在确定洛伐他汀在两种鼠类疼痛模型中的抗痛觉特性,以及阿片类拮抗剂(纳曲酮、纳曲吲哚、去甲斑蝥素)、利培酮和 L-NAME(L-NG-硝基精氨酸甲酯)在这一效应中的参与情况。之所以在现有的他汀类药物中选择瑞舒伐他汀,是因为它是常用的处方药,具有较高的效力、疗效和可接受的安全性。在注射阿片类拮抗剂、利培酮和 L-NAME 之前和之后,通过剂量反应曲线对醋酸蠕动试验和福尔马林后爪试验中瑞舒伐他汀的抗痛觉作用进行了评估。这项研究表明,在这两种实验性鼠痛试验中,所检测的药物都会调节罗伐他汀的抗痛觉作用。洛伐他汀的抗痛觉作用可能是由于阿片类拮抗剂利培酮和L-NAME的特殊调节作用所致。鉴于洛伐他汀的广泛作用,本研究结果可能对疼痛治疗具有新的临床意义。
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