Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice
Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice
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DOI：
10.1016/j.neuropharm.2006.05.003
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发表时间：
2006-09-01
影响因子：
4.7
通讯作者：
Yanai, Kazuhiko
中科院分区：
文献类型：
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作者：
Mobarakeh, Jalal Izadi;Takahashi, Kazuhiro;Yanai, Kazuhiko
我们以前已经表明，吗啡的抗伤害作用增强组胺H I受体基因敲除小鼠。本研究采用组胺H2受体基因敲除（H2KO）小鼠和组胺H2受体拮抗剂，研究了脊髓上组胺H2受体在吗啡抗伤害作用中的作用。通过热刺激（热板、甩尾和缩爪试验）、机械刺激（尾压试验）和化学刺激（福尔马林和辣椒素试验）试验评价抗伤害感受。H2KO小鼠的疼痛感知阈值高于野生型小鼠。与野生型小鼠相比，H2 KO小鼠脑室注射吗啡的抗伤害作用增强。与单独使用吗啡或西咪替丁相比，侧脑室联合使用吗啡和西咪替丁在野生型小鼠中产生了显著的抗伤害作用。此外，zolantidine，一种选择性和疏水性H2受体拮抗剂，增强了吗啡在所有伤害性试验的影响。这些结果表明，组胺通过脊髓上水平的H2受体对吗啡诱导的抗伤害作用发挥抑制作用。我们目前和以前的研究表明，H1和H2受体协同作用，以调节中枢神经系统的疼痛感知。(c)2006爱思唯尔有限公司版权所有。
We have previously shown that antinociceptive effects of morphine are enhanced in histamine H I receptor gene knockout mice. In the present study, involvement of supraspinal histamine H2 receptor in antinociception by morphine was examined using histamine H2 receptor gene knockout (H2KO) mice and histamine H-2 receptor antagonists. Antinociception was evaluated by assays for thermal (hot-plate, tail-flick and paw-withdrawal tests), mechanical (tail-pressure test) and chemical (formalin and capsaicin tests) stimuli. Thresholds for pain perception in H2KO mice were higher than wild-type mice. Antinociceptive effects of intracerebroventricularly administered morphine were enhanced in the H2KO mice compared to wild-type mice. Intracerebroventricular co-administration of morphine and cimetidine produced significant antinociceptive effects in the wild-type mice when compared to morphine or cimetidine alone. Furthermore, zolantidine, a selective and hydrophobic H2 receptor antagonist, enhanced the effects of morphine in all nociceptive assays examined. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H2 receptors at the supraspinal level. Our present and previous studies suggest that H1 and H2 receptors cooperatively function to modulate pain perception in the central nervous system. (c) 2006 Elsevier Ltd. All rights reserved.