Effects of the combined continuous administration of morphine and the high-efficacy 5-HT1A agonist, F 13640 in a rat model of trigeminal neuropathic pain
Effects of the combined continuous administration of morphine and the high-efficacy 5-HT1A agonist, F 13640 in a rat model of trigeminal neuropathic pain
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DOI：
10.1016/j.ejpain.2004.01.002
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发表时间：
2004-12-01
影响因子：
3.6
通讯作者：
Colpaert, FC
中科院分区：
文献类型：
--
作者：
Deseure, KR;Adriaensen, HF;Colpaert, FC
f13640是最近发现的一种高效5-HT1A受体激动剂，在三叉神经性疼痛大鼠模型中，急性和持续给药显示出强大的抗异动作用。在该模型中，连续输注吗啡（5mg /天）在给药的第一周显示有效，但在第二周结束时几乎完全无效；f13640的有效性（0.63 mg/天）在两周内保持不变。本实验观察f13640与吗啡联合输注对小鼠的影响。在第一周内，两种药物联合使用产生的效果与单独给药时的吗啡相似，比单独给药时的效果更大。在第二周，联合用药产生的效果与单独使用f13640相似，比单独使用吗啡更有效。后一组数据表明，5-HT1A激动剂F 13640在该模型中抑制吗啡耐受的发展。然而，也有可能阿片类药物与5-HT1A受体激活所启动的不同机制之间很少（如果有的话）发生相互作用，并且在两周治疗期结束时仍然存在的抗异动作用仅仅是由于5-HT1A受体激活。F 13640在治疗第二周的稳定效果超过吗啡，并且在F 13640的基础上添加吗啡并没有改善。(C) 2004年国际疼痛研究协会欧洲分会联合会。Elsevier Ltd.出版。版权所有。
F 13640 is a recently discovered high-efficacy 5-HT1A receptor agonist that has demonstrated robust anti-allodynic efficacy in a rat model of trigeminal neuropathic pain upon acute and continuous administration. In this model, continuous morphine infusion (5 mg/day) was shown to be effective during the first week of its administration but became almost completely ineffective by the end of the second week; F 13640's effectiveness (0.63 mg/day) remained unchanged during two weeks. Here, we examined the effects of combining F 13640 infusion with that of morphine. During the first week, the combination of the two agents produced a magnitude of effect that was similar to that of morphine when given alone and larger than that of F 13640 alone. During the second week, the combination produced an effect that was similar to that of F 13640 alone, and more effective than that of morphine alone. The latter data suggest that the 5-HT1A agonist, F 13640, inhibits the development of tolerance to morphine in this model. However, it is also possible that little, if any, interaction occurred between the different mechanisms initiated by opioid and 5-HT1A receptor activation, and that the anti-allodynic effect that remained by the end of the two-week treatment period is due solely to 5-HT1A receptor activation. The stable effects of F 13640 during the second week of treatment surpassed those of morphine and were not improved by the addition of morphine to F 13640. (C) 2004 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.