School of Medicine, Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Independencia 1027, Clasificador 70.000, Santiago 7, Chile.
Pharmacol Rep. 2011;63(2):433-40. doi: 10.1016/s1734-1140(11)70509-6.
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the management of acute and chronic pain. The role of the opioid system in the synergism between NSAIDs is not well characterized. Mice were injected with a 5% formalin solution (20 μl) into the upper right lip to perform an orofacial formalin test. The isobolographic method was used to determine the interaction between dexketoprofen, which is the (S)-(+) enantiomer of ketoprofen, and meloxicam co-administration. Additionally, the non-selective, opioid antagonist naltrexone, the selective δ opioid receptor (DOP) antagonist naltrindole and the selective κ opioid receptor (KOP) antagonist norbinaltorphimine were used to assess the opioid effects on this interaction. Intraperitoneal administration of dexketoprofen or meloxicam induced dose-dependent antinociception with different phase I and phase II potencies in the orofacial formalin test. Meloxicam displayed similar potencies (ED(50)) in phase I (7.20 mg/kg) and phase II (8.60 mg/kg). Dexketoprofen was more potent in phase I (19.96 mg/kg) than in phase II (50.90 mg/kg). The interactions between dexketoprofen and meloxicam were synergistic in both phases. This was determined based on the fixed ratios (1:1) of their ED(50) values, which were determined by isobolographic analysis. Furthermore, this antinociceptive activity does not seem to be modulated by opioid receptor blockers because they did not induce changes in the nature of this interaction. This finding may be relevant with regards to NSAID multi-modal analgesia where an opioid antagonist must be used.
非甾体抗炎药（NSAIDs）是用于治疗急性和慢性疼痛的最广泛使用的药物之一。阿片样物质系统在 NSAIDs 协同作用中的作用尚未得到很好的描述。将 5%福尔马林溶液（20 μl）注射到上唇中来进行口腔福尔马林测试。使用等辐射法来确定右旋酮洛芬（酮洛芬的（S）-（+）对映异构体）与美洛昔康共同给药之间的相互作用。此外，还使用了非选择性阿片受体拮抗剂纳曲酮、选择性 δ 阿片受体（DOP）拮抗剂纳曲吲哚和选择性 κ 阿片受体（KOP）拮抗剂诺比那嗪来评估阿片受体对这种相互作用的影响。腹腔内给予右旋酮洛芬或美洛昔康可诱导口腔福尔马林测试中剂量依赖性的镇痛作用，且具有不同的 I 相和 II 相效力。美洛昔康在 I 相（7.20 mg/kg）和 II 相（8.60 mg/kg）中的效力相似。右旋酮洛芬在 I 相（19.96 mg/kg）比在 II 相（50.90 mg/kg）中更有效。右旋酮洛芬和美洛昔康在 I 相和 II 相均表现出协同作用。这是根据等辐射分析确定的它们的 ED50 值的固定比例（1:1）来确定的。此外，这种镇痛活性似乎不受阿片受体阻滞剂的调节，因为它们不会改变这种相互作用的性质。这一发现可能与 NSAID 多模式镇痛有关，在这种情况下必须使用阿片受体拮抗剂。
