Synergistic antinociceptive effects of ketamine and morphine in the orofacial capsaicin test in the rat
Synergistic antinociceptive effects of ketamine and morphine in the orofacial capsaicin test in the rat
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DOI：
10.1097/00000542-200310000-00033
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发表时间：
2003-10-01
期刊：
影响因子：
8.8
通讯作者：
Pelissier, T
中科院分区：
文献类型：
--
作者：
Alvarez, P;Saavedra, G;Pelissier, T
背景资料：非竞争性N-甲基-D-天冬氨酸受体拮抗剂氯胺酮治疗口面疼痛的临床疗效已有报道。然而，与拟精神障碍相关的副作用限制了氯胺酮作为镇痛剂的使用。从理论上讲，这种限制可以通过使用低剂量的氯胺酮与其他镇痛药联合使用来最大限度地减少。在本研究中，氯胺酮和吗啡在orofacial辣椒素在rats.Methods：雄性SD大鼠皮下注射溶剂，氯胺酮，吗啡，或两种药物的组合之间的潜在协同抗伤害性相互作用进行了调查。30分钟后，通过将1.5 μ g/25穆尔溶液注射到触须垫中进行口面辣椒素试验。将动物行为记录在录像带上并离线分析。在42 min的时间内测量用于摩擦-抓挠伤害性行为的总时间。皮下注射氯胺酮（0.4、1.25、4、12.5 mg/kg）、吗啡氯胺酮+吗啡（0.20 ± 0.12，0.40 ± 0.24，0.80 ± 0.49，1.61 ± 0.97，3.21 ± 1.94 mg/kg）可剂量依赖性地减少大鼠的面部摩擦-抓挠行为。等辐射线分析表明，氯胺酮+吗啡协会抑制了研究的行为在一个superadditive mathematics.Conclusions：这些结果表明，氯胺酮和吗啡具有抗伤害性的影响orofacial辣椒素测试。此外，它们的组合产生协同抗伤害感受。因此，这表明，氯胺酮和吗啡一起使用时，在较低的剂量下可能比目前单独给药时使用的剂量更有效。这可能会提供一个有用的策略，口面疼痛的临床管理。
Background: The clinical efficacy of the noncompetitive N-methyl-D-aspartate receptor antagonist ketamine for treating orofacial pain has already been reported. Side effects related to psychotomimetic disturbances, however, limit ketamine use as an analgesic. Theoretically, this limitation could be minimized by using low doses of ketamine in combination with other analgesics. In the present study, the potential synergistic antinociceptive interaction between ketamine and morphine in the orofacial capsaicin test in rats was investigated.Methods: Male Sprague-Dawley rats were subcutaneously injected with solvent, ketamine, morphine, or combination of both drugs. Thirty minutes later, the orofacial capsaicin test was performed by injecting of 1.5 mug/25 mul of a capsaicin solution into the vibrissa pad. Animal behavior was recorded on video-tape and analyzed off-line. The total time spent on rubbing-scratching nociceptive behavior during a period of 42 min was measured.Results: Subcutaneously administered ketamine (0.4, 1.25, 4, 12.5 mg/kg), morphine (0.5, 1, 2, 4 mg/kg) and ketamine + morphine (0.20 + 0.12, 0.40 + 0.24, 0.80 + 0.49, 1.61 + 0.97, 3.21 + 1.94 mg/kg) reduced the rat facial rubbing-scratching behavior in a dose-dependent manner. Isobolographic analysis showed that the ketamine + morphine association inhibited the studied behavior in a superadditive manner.Conclusions: These results indicate that ketamine and morphine have antinociceptive effects on the orofacial capsaicin test. Furthermore, their combination produces synergistic antinociception. It is therefore suggested that, used together, ketamine and morphine might be clinically efficient at lower doses than those currently used when administered separately. This could provide a useful strategy for the clinical management of orofacial pain.