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Investigation for mechanism of morphine-inducing spastic paraplegia after a non-injurious interval of spinal cord ischemia

脊髓缺血非损伤性间歇期吗啡诱发痉挛性截瘫机制的探讨

基本信息

批准号：
16591551
负责人：
KAKINOHANA Manabu
金额：
$ 2.11万
依托单位：
University of the Ryukyus
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591551/
关键词：
spinal cord ischemia opioid spastic paraplegia 大動脈手術対麻痺モルヒネ

项目摘要

(1) Although intra hecal (IT) morphine after a short interval of aortic occlusion in a rodent model induced transient spastic paraparesis via opioid receptor-coupled effects in spinal cord, investigations on the relationship between the activation of opioid receptor subtypes and neurological function after spinal cord ischemia have not been reported. To determine the role of these opioid receptors in spinal mechanisms of motor dysfunction after spinal cord ischemia we investigated whether IT administration of various opioid receptor agonists can induce paraparesis after a noninjurious interval of spinal cord ischemia in rats. In Sprague-Dawley rats implanted with an IT catheter, spinal cord ischemia was induced for 6 min using an intraaortic balloon. Mu ([D-Ala^2, N-Me Phe^4, Gly-ol^5] enkephalin), kappa (U50488H) or delta (p-Pen^<2,5>] enkephalin) agonist was injected intrathecally at 30 min after reflow. A separate group of animals was used to investigate the dose-response effect on … More this motor dysfunction. For this purpose, three doses of mu, kappa, or delta agonist were injected intrathecally after ischemia. After IT injection, recovery of motor function was assessed periodically using the motor deficit index (0 = complete recovery; 6 = complete paraplegia). IT administration of mu and delta but not kappa agonists produced dose-dependent effects in induction of spastic paraparesis in the rat. In addition, this spasticity induced by IT mu and delta agonists was reversed completely by IT naloxone and naltrindole, respectively. These results suggested that the effect of various opioids on motor function after a noninjurious interval of spinal cord ischemia depends upon individual opioid receptor subtypes.(2) The purpose of this study is to investigate the interaction between K+ATP channel opener (nicorandil) and morphine on motor function after non-injurious interval of spinal cord ischemia in the rat. Spinal ischemia was induced by aortic occlusion for 6 min with a balloon catheter in Sprague-Dawley rats. All animals received intrathecal injection of morphine (1-60 μg) 1 h after ischemia. In addition to the intrathecal injection of morphine, group M (control animals), group MN (combination of morphine and nicorandil), and group MNG (combination of morphine, nicorandil, and glibenclamide) received intrathecal saline, nicorandil (10 μg) and both glibenclamide (10 μg) and nicorandil (10 μg) after 150 min of reperfusion, respectively. The quintal bioassay for the effect of intrathecal morphine on neurological function after ischemia was performed to calculate 50% effective dose values (ED_<50>) for inducing paraparesis at 3 h of reperfusion. The ED_<50> in the group M and group MN was 15.1± 4.9 μg and 2.9± 1.0 μg of IT morphine respectively (p < 0.05). In Group MNG, the dose-response curve shifted back to the right and the ED_<50> for inducing paraparesis was 11.6 ± 4.7 μg of IT morphine. The present study suggests that intrathecal low dose morphine combined with nicoranil could induce spastic paraparesis after non-injurious interval of spinal cord ischemia in the rat. Less

(1)虽然在啮齿动物模型中，主动脉阻断后短时间内注射（IT）吗啡通过脊髓中的阿片受体偶联效应引起短暂痉挛性轻瘫，但关于脊髓缺血后阿片受体亚型激活与神经功能之间关系的研究尚未报道。为了确定这些阿片受体在脊髓缺血后运动功能障碍的脊髓机制中的作用，我们研究了在大鼠脊髓缺血的非损伤性间隔后，IT给药各种阿片受体激动剂是否可以诱导轻瘫。在植入IT导管的Sprague-Dawley大鼠中，使用主动脉内球囊诱导脊髓缺血6分钟。在复流后30 min鞘内注射Mu（[D-Ala^2，N-Me Phe ^4，Gly-ol^5]脑啡肽）、kappa（U 50488 H）或delta（p-Pen^<2，5>]脑啡肽）激动剂。使用单独的一组动物来研究剂量-反应效应。 ...更多信息这种运动功能障碍为此，在缺血后鞘内注射三个剂量的μ、κ或δ激动剂。注射IT后，使用运动缺陷指数定期评估运动功能的恢复（0 =完全恢复; 6 =完全截瘫）。IT给予mu和δ激动剂而非κ激动剂在诱导大鼠痉挛性轻瘫方面产生剂量依赖性效应。此外，这种痉挛诱导的IT亩和δ激动剂完全逆转IT纳洛酮和纳曲吲哚，分别。这些结果表明，在脊髓缺血的非损伤性间隔后，各种阿片类药物对运动功能的影响取决于个体阿片受体亚型。(2)本研究旨在探讨钾ATP通道开放剂尼可地尔与吗啡对大鼠脊髓缺血后运动功能的相互作用。在Sprague-Dawley大鼠中，通过用球囊导管阻断主动脉6分钟来诱导脊髓缺血。缺血后1h鞘内注射吗啡（1-60 μg）。除鞘内注射吗啡外，M组（对照组）、MN组（吗啡和尼可地尔联合用药组）和MNG组（吗啡、尼可地尔和格列本脲联合用药组）在再灌注150 min后分别鞘内注射生理盐水、尼可地尔（10 μ g）以及格列本脲（10 μg）和尼可地尔（10 μg）。采用五分法测定鞘内注射吗啡对缺血后神经功能的影响，计算<50>再灌注3 h时诱导下肢轻瘫的50%有效剂量值（艾德_）。M<50>组和MN组的艾德_（ED）分别为15.1± 4.9 μg和2.9± 1.0 μg（p < 0.05）。MNG组剂量-反应曲线右移，诱发下肢轻瘫的艾德_（ED）<50>为11.6 ± 4.7 μg。本研究提示，鞘内注射小剂量吗啡和尼可拉尼尔可诱发大鼠脊髓缺血非损伤性间歇期后痉挛性轻瘫。少

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intrathecal nicorandil and small-dose morphine can induce spastic paraparesis after a moninjurious interval of spinal cord ischemia in the rat.

鞘内注射尼可地尔和小剂量吗啡可在大鼠脊髓缺血短暂损伤后引起痉挛性截瘫。

DOI：
发表时间：
2006
期刊：
Anesth Analg 102・4
影响因子：
0
作者：
Kakinohana M;Nakamura S;Miyata Y;et al.;T.Fuchigami et al.
通讯作者：
T.Fuchigami et al.

Level of consciousness affects the excitability of spinal motor neurons during propofol sedation in human.

意识水平影响人异丙酚镇静期间脊髓运动神经元的兴奋性。

DOI：
发表时间：
2006
期刊：
Br J Anaesth 96・6
影响因子：
0
作者：
高橋徹;森田潔;田中信彦;田中信彦;T Fuchigami et al.;M Kakinohana et al.;M Kakinohana et al.;M Kakinohana et al.
通讯作者：
M Kakinohana et al.

Intrathecal nicorandil and small-dose morphine can induce spastic paraparesis after a noninjurious interval of spinal cord ischemia in the rat