Effects of rat/mouse hemokinin-1, a mammalian tachykinin peptide, on the antinociceptive activity of pethidine administered at the peripheral and supraspinal level
Effects of rat/mouse hemokinin-1, a mammalian tachykinin peptide, on the antinociceptive activity of pethidine administered at the peripheral and supraspinal level
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DOI：
10.1016/j.bbr.2007.06.019
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发表时间：
2007-11-22
影响因子：
2.7
通讯作者：
Wang, Rui
中科院分区：
文献类型：
--
作者：
Fu, Cai-Yun;Tang, Xiao-Long;Wang, Rui
我们最近报道，大鼠/小鼠血激肽-1（r/mHK- 1），哺乳动物速激肽，产生剂量和时间相关的镇痛作用在脊髓上水平通过激活NK 1受体。此外，r/mHK-1显着提高了镇痛的程度和持续时间的吗啡给药在外周和脊髓上水平通过阿片样物质的反应神经元的药理作用的收敛。盐酸哌替啶是一种重要的麻醉性镇痛药，具有阿片激动剂的作用，药理作用与吗啡相似。为进一步了解哌替啶的药理作用，本研究旨在通过比较r/mHK-1与吗啡的伤害性感受，探讨r/mHK与哌替啶之间的关系。我们的数据表明，r/mHK-1显着增强哌替啶在外周水平的抗伤害性感受程度，但在脊髓上的水平。这些抗伤害性作用被经典阿片受体拮抗剂纳洛酮预先治疗阻断，表明增强的镇痛作用是由阿片样物质反应神经元介导的。哌替啶和吗啡与r/mHK- 1组合的抗伤害感受活性的差异是因为哌替啶和吗啡的物理化学和药代动力学性质，特别是它们的亲脂性存在差异。我们的研究结果可能为控制疼痛的新策略铺平道路，并可能提供一种临床策略，以优先选择阿片类药物。(C)2007 Elsevier B. V.保留所有权利。
We have recently reported that rat/mouse hemokinin-1 (r/m HK- 1), a mammalian tachykinin, produced dose- and time-related antinociceptive effects at the supraspinal level via activating NK1 receptors. Moreover, r/m HK-1 remarkably enhanced both the antinociceptive extent and duration of morphine administered at the peripheral and supraspinal level through a convergence of pharmacological effects of opioid-responsive neurons. Pethidine hydrochloride is an important narcotic analgesic, which acts as an opiate agonist and has pharmacological effects similar to morphine. To improve our knowledge of the pharmacology of pethidine, the aim of the present study was to investigate the relationship between the nociception of r/m HK and pethidine by comparing it with that of r/m HK-1 and morphine. Our data showed that r/m HK-1 remarkably enhanced the antinociceptive extent of pethidine administered at the peripheral level, but not at the supraspinal level. These antinociceptive effects were blocked by prior treatment with the classical opioid receptor antagonist naloxone, indicating that the potentiated analgesic effect is mediated by opioid-responsive neurons. Differences in the antinociceptive activity of pethidine and morphine in combination with r/m HK- 1, arise because there are differences in the physicochemical and pharmacokinetic properties of pethidine and morphine, particularly their lipophilicity. Our results may pave the way for a new strategy for the control of pain and may provide a clinical strategy to enable selection of either opioid as a priority. (C) 2007 Elsevier B.V. All rights reserved.