Miranda Hugo F, Prieto Juan Carlos, Pinardi Gianni
Phramacology Program, ICBM, Faculty of Medicine, University of Chile, PO Box 70.000, Santiago 7, Chile.
Brain Res. 2005 Jul 12;1049(2):165-70. doi: 10.1016/j.brainres.2005.04.068.
The antinociception induced by the intrathecal coadministration of combinations of morphine with the nonsteroidal anti-inflammatory drugs (NSAIDs) naproxen, piroxicam, metamizol, diclofenac and ketoprofen was studied by isobolographic analysis in the acetic acid writhing test of mice. The effective dose that produced 50% antinociception (ED(50)) was calculated from the log dose-response curve of intrathecally administered fixed ratio combinations of morphine with each NSAID. By isobolographic analysis, this ED(50) was compared to the theoretical additive ED(50) calculated from the ED(50) of morphine and of each NSAID alone. As shown by isobolograms, all the combinations were synergistic, the experimental ED(50)'s being significantly smaller than the theoretically calculated ED(50)'s. The results of this study demonstrate potent interactions between morphine and NSAIDs and validate the clinical use of the combinations of opioids and NSAIDs in pain treatment, even by the intrathecal route.
通过小鼠醋酸扭体试验中的等效应线分析，研究了鞘内联合给予吗啡与非甾体抗炎药（NSAIDs）萘普生、吡罗昔康、安乃近、双氯芬酸和酮洛芬所诱导的抗伤害感受作用。从鞘内给予吗啡与每种NSAIDs的固定比例组合的对数剂量-反应曲线计算出产生50%抗伤害感受的有效剂量（ED50）。通过等效应线分析，将该ED50与由吗啡和每种NSAIDs单独的ED50计算出的理论相加ED50进行比较。如等效应线所示，所有组合均具有协同作用，实验性ED50显著小于理论计算的ED50。本研究结果证明了吗啡与NSAIDs之间的强效相互作用，并验证了阿片类药物与NSAIDs联合用于疼痛治疗（即使是通过鞘内途径）的临床应用。
