Morphine, oxycodone, methadone and its enantiomers in different models of nociception in the rat
Morphine, oxycodone, methadone and its enantiomers in different models of nociception in the rat
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DOI：
10.1213/01.ane.0000205751.88422.41
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发表时间：
2006-06-01
影响因子：
5.7
通讯作者：
Kalso, Eija
中科院分区：
文献类型：
--
作者：
Lemberg, Kim;Kontinen, Vesa K.;Kalso, Eija
我们研究了常用的g-阿片受体激动剂吗啡、羟考酮、美沙酮和美沙酮的对映体在急性疼痛的热和机械模型以及大鼠神经性疼痛的脊神经结扎模型中的作用。皮下注射吗啡、羟考酮和美沙酮在甩尾、热板和爪压测试中产生剂量依赖性的镇痛作用。 L-美沙酮、外消旋美沙酮和羟考酮具有相似的剂量依赖性镇痛作用，而吗啡的剂量反应曲线较浅。在神经性疼痛的脊髓神经结扎模型中，皮下注射吗啡、羟考酮、美沙酮和L-美沙酮在机械性和冷性异常性疼痛测试中具有抗异常性疼痛作用。左旋美沙酮在受试药物中表现出最强的抗异常疼痛作用。 d-美沙酮在所有测试中均无效。吗啡5.0 mg/kg、羟考酮2.5 mg/kg和l-美沙酮1.25 mg/kg在给药后30分钟减少自发运动。总之，在急性伤害感受中，所有μ阿片受体激动剂均产生抗伤害感受，其中吗啡的作用最弱。在神经损伤疼痛方面，与其他阿片类药物相比，左旋美沙酮在机械性和冷性异常性疼痛方面均表现出最大的抗异常性疼痛效力。阿片类药物在不同的疼痛模型中似乎有不同的特征。应该研究左旋美沙酮对人类神经性疼痛的作用。
We studied the effects of the commonly used g-opioid receptor agonists morphine, oxycodone, methadone and the enantiomers of methadone in thermal and mechanical models of acute pain and in the spinal nerve ligation model of neuropathic pain in rats. Subcutaneous administration of morphine, oxycodone, and methadone produced a dose-dependent antinociceptive effect in the tail flick, hotplate, and paw pressure tests. l-methadone, racemic methadone, and oxycodone had a similar dose-dependent antinociceptive effect, whereas the dose-response curve of morphine was shallower. In the spinal nerve ligation model of neuropathic pain, subcutaneous administration of morphine, oxycodone, methadone and l-methadone had antiallodynic effects in tests of mechanical and cold allodynia. l-methadone showed the strongest antiallodynic effect of the tested drugs. d-methadone was inactive in all tests. Morphine 5.0 mg/kg, oxycodone 2.5 mg/kg, and l-methadone 1.25 mg/kg decreased spontaneous locomotion 30 min after drug administration. In conclusion, in acute nociception all mu-opioid receptor agonists produced antinociception, with morphine showing the weakest effect. In nerve injury pain, l-methadone showed the greatest antiallodynic potency in both mechanical and cold allodynia compared with the other opioids. Opioids seem to have different profiles in different pain models. l-methadone should be studied for neuropathic pain in humans.