Enhancement of morphine antinociception with the peptide N-methyl-D-aspartate receptor antagonist [Ser1]-histogranin in the rat formalin test
Enhancement of morphine antinociception with the peptide N-methyl-D-aspartate receptor antagonist [Ser1]-histogranin in the rat formalin test
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DOI：
10.1016/j.brainres.2006.04.012
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发表时间：
2006-06-20
期刊：
影响因子：
2.9
通讯作者：
Sagen, Jacqueline
中科院分区：
文献类型：
--
作者：
Hama, Aldric;Basler, Adam;Sagen, Jacqueline
阿片类药物可用于减轻慢性疼痛，但长期使用会因疼痛可能随时间增加、剂量需求增加和不良副作用而变得复杂。阿片类药物中可加入氯胺酮（一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂）等辅助剂，以提供更一致的镇痛效果。然而，NMDA受体拮抗剂的不希望的运动副作用阻止了它们的广泛临床应用。在本研究中，评价了一种天然衍生肽histogranin的类似物[Ser（1）] histogranin（SHG），一种NMDA受体调节剂，没有目前临床使用的不良副作用，在大鼠福尔马林试验中评价了其增强鞘内吗啡的抗伤害作用的潜力。鞘内注射SHG和吗啡的组合导致在第一和第二阶段中与单独的吗啡相比显著减少后爪退缩。当单独测试时，组合中使用的SHG的有效剂量没有功效。这些结果类似于氯胺酮和吗啡组合获得的增加的功效。因此，使用具有潜在改善的安全性特征的新型肽NMDA受体调节剂可以增强阿片类药物的功效。(c)2006 Elsevier B. V.保留所有权利。
Opiates may be used to attenuate chronic pain, but long-term use is complicated by the possible increase in pain over time, escalating dose requirements, and untoward side effects. Adjuncts such as ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may be added to opiates to provide more consistent analgesia. However, the unwanted motor side effects of NMDA receptor antagonists prevent their widespread clinical usage. In the current study, an analogue of the naturally-derived peptide histogranin, [Ser(1)] histogranin (SHG), an NMDA receptor modulator without adverse side effects like those in current clinical use, was evaluated for its potential to enhance the antinociceptive effect of intrathecal morphine in the rat formalin test. Intrathecal injection of a combination of SHG and morphine resulted in significantly reduced hind paw flinching compared with morphine alone in the first and second phases. The effective dose of SHG used in the combination had no efficacy when tested alone. These results were similar to the increased efficacy that was obtained with a combination of ketamine and morphine. Thus, enhancement of opiate efficacy is possible using a novel peptide NMDA receptor modulator with a potentially improved safety profile. (c) 2006 Elsevier B.V. All rights reserved.