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）尽管在啮齿动物模型中短时间间隔闭塞后，hecal（IT）吗啡在脊髓中通过阿片类受体偶联作用引起的瞬态痉挛性瘫痪，但尚未据报道，研究阿片类脊髓性脊髓质性和神经性功能的激活之间的关系。为了确定这些阿片类受体在脊髓缺血后的作用在运动功能障碍的脊柱机制中，我们研究了在大鼠中脊髓局部缺血间隔后，其IT施用各种阿片受体是否可以诱导旁皮。在植入IT导管的Sprague-Dawley大鼠中，使用船长气球诱导脊髓缺血6分钟。 Mu（[d-ala^2，n-me phe^4，gly-ol^5] enkephalin），kappa（u50488h）或delta（p-pen^<2,5>] enkephalin）激动剂在回流后30分钟被静脉注射。一组动物用于研究……更多此运动功能障碍的剂量反应效应。为此，在缺血后静定地注入了三剂MU，Kappa或Delta激动剂。注射后，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 =完全的截瘫）。 MU和Delta的IT给药，但没有Kappa激动剂产生剂量依赖性大鼠的痉挛性诱导。另外，IT MU和Delta激动剂引起的这种痉挛分别被IT纳洛酮和Naltrindole完全逆转。这些结果表明，各种阿片类药物在脊髓缺血间隔不舒适的间隔后对运动功能的影响取决于单个阿片类受体的亚型。（2）这项研究的目的是研究K+ATP Channel开瓶器（Nicorandil）和吗啡之间的相互作用，并在无炎症间隔后的脊髓质质量Ischemia in Cathemia in Cary n of Cary n of car n of Cary n of car n of Math n of car。脊柱缺血是通过主动脉闭塞诱导的6分钟，在Sprague-Dawley大鼠中用气球导管诱导。缺血后1小时，所有动物接受吗啡鞘内注射（1-60μg）。除鞘内注射吗啡外，M组（对照动物），MN组（吗啡和尼古兰）组以及MNG组（吗啡，尼古兰il和glibenclamide的组合）接受了内颗粒盐盐的盐水，盐酸盐，Nicorandil（10 ig）（10iμg）和Glibenclamife 分别。进行缺血后鞘内吗啡对神经功能功能的影响的五重生物测定进行了计算在再灌注3 h时诱导的副群的50％有效剂量值（ED_ <50>）。组M和组MN中的ED_ <50>为15.1±4.9μg和2.9±1.0μg的IT吗啡，在MNG组中，剂量反应曲线向右移回右侧，用于诱导Paraparasis的ED_ <50>为11.6±4.7g IT Morphine。本研究表明，鞘内的低剂量吗啡与尼古拉尼尔结合在大鼠中脊髓缺血的无伤性间隔后会诱导痉挛性旁皮。较少的

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.

Mu and Delta, but not Kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rat.

阿片类激动剂 Mu 和 Delta（但不是 Kappa）会在大鼠短暂脊髓缺血后诱发痉挛性截瘫。

DOI：
发表时间：
2006
期刊：
Br J Anaesth 96・1
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.
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

DOI：
10.1213/01.ane.0000198634.25504.83
发表时间：
2006-04-01
期刊：
ANESTHESIA AND ANALGESIA
影响因子：
5.7
作者：
Fuchigami, T;Kakinohana, M;Sugahara, K
通讯作者：
Sugahara, K

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.

Myogenic Transcranial Motor Evoked Potentials Monitoring Cannot Always Predict Neurological Outcome After Spinal Cord Ischemia In Rats.

肌源性经颅运动诱发电位监测不能总能预测大鼠脊髓缺血后的神经系统结果。