• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2006 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number 16591551
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionUniversity of the Ryukyus

Principal Investigator

KAKINOHANA Manabu  University of the Ryukyus, Faculty of Medicine, Associate professor-, 医学部, 助教授 (20274897)

Co-Investigator(Kenkyū-buntansha) NARITA Minoru  Hoshi University School of Pharmacy and Pharmaceutical Sciences, Toxicology, Associate professor, 薬学部, 助教授 (40318613)
Project Period (FY) 2004 – 2006
Keywordsspinal cord ischemia / opioid / spastic paraplegia
Research Abstract

(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

  • Research Products

    (10 results)

All 2006 2005

All Journal Article (10 results)

  • [Journal Article] Intrathecal nicorandil and small-dose morphine can induce spastic paraparesis after a noninjurious interval of spinal cord ischemia in the rat.2006

    • Author(s)
      T Fuchigami et al.
    • Journal Title

      Anesth Analg 102・4

      Pages: 1217-1222

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mu and Delta, but not Kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rat.2006

    • Author(s)
      M Kakinohana et al.
    • Journal Title

      Br J Anaesth 96・1

      Pages: 88-94

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Influence of the descending thoracic aortic cross clamping on bispectral index value and plasma propofol concentration in humans.2006

    • Author(s)
      M Kakinohana et al.
    • Journal Title

      Anesthesiology 104・5

      Pages: 939-943

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Level of consciousness affects the excitability of spinal motor neurons during propofol sedation in human.2006

    • Author(s)
      M Kakinohana et al.
    • Journal Title

      Br J Anaesth 96・6

      Pages: 742-746

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Intrathecal nicorandil and small-dose morphine can induce spastic paraparesis after a noninjurious interval of spinal cord ischemia in the rat2006

    • Author(s)
      T Fuchigami, et al.
    • Journal Title

      Anesth Analg 102・4

      Pages: 1217-1222

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mu and Delta, but not Kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischemia in rat.2006

    • Author(s)
      M Kakinohana, et al.
    • Journal Title

      Br J Anaesth 96・1

      Pages: 88-94

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Influence of the descending thoracic aortic cross clamping on bispectral index value and plasma propofol concentration in humans.2006

    • Author(s)
      M Kakinohana, et al.
    • Journal Title

      Anesthesiology 104・5

      Pages: 939-943

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Level of consciousness affects the excitability of spinal motor neurons during propofol sedation in human.2006

    • Author(s)
      M Kakinohana, et al.
    • Journal Title

      Br J Anaesth 96・6

      Pages: 742-746

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Myogenic transcranial motor evoked potentials monitoring can not always predict neurological outcome after spinal cord ischemia in rats.2005

    • Author(s)
      M Kakinohana et al.
    • Journal Title

      J Thorac Cardiovasc Surg 129・1

      Pages: 46-52

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Myogenic transcranial motor evoked potentials monitoring can not always predict neurological outcome after spinal cord ischemia in rats.2005

    • Author(s)
      M Kakinohana, et al.
    • Journal Title

      J Thorac Cardiovasc Surg 1291・1

      Pages: 46-52

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2008-05-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi