Fu Cai-Yun, Tang Xiao-Long, Yang Qi, Chen Qiang, Wang Rui
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
Behav Brain Res. 2007 Nov 22;184(1):39-46. doi: 10.1016/j.bbr.2007.06.019. Epub 2007 Jun 29.
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 NK(1) 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.
我们最近报道，大鼠/小鼠速激肽-1（r/m HK-1），一种哺乳动物速激肽，通过激活NK(1)受体在脊髓上水平产生剂量和时间相关的抗伤害感受作用。此外，r/m HK-1通过阿片样物质反应性神经元的药理作用汇聚，显著增强了在外周和脊髓上水平给予吗啡的抗伤害感受程度和持续时间。盐酸哌替啶是一种重要的麻醉性镇痛药，它作为阿片类激动剂，具有与吗啡相似的药理作用。为了增进我们对哌替啶药理学的了解，本研究的目的是通过将r/m HK与r/m HK-1和吗啡进行比较，研究r/m HK与哌替啶伤害感受之间的关系。我们的数据表明，r/m HK-1显著增强了在外周水平给予哌替啶的抗伤害感受程度，但在脊髓上水平则没有。这些抗伤害感受作用被经典阿片受体拮抗剂纳洛酮预先处理所阻断，表明增强的镇痛作用是由阿片样物质反应性神经元介导的。哌替啶和吗啡与r/m HK-1联合使用时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存在差异，特别是它们的亲脂性。我们的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，以便能够优先选择其中一种阿片类药物。
