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2006 Fiscal Year Final Research Report Summary

Implication of brain and spinal protein kinase C in the suppression of morphine-induced rewarding effect under a neuropathic pain

Research Project

Project/Area Number 16591530
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionUniversity of Toyama (2005-2006)
Toyama Medical and Pharmaceutical University (2004)

Principal Investigator

YAMAZAKI Mitsuaki  University of Toyama, Anesthesiology, Professor, 医学部, 教授 (70158145)

Co-Investigator(Kenkyū-buntansha) SASAKI Rika  University of Toyama, Anesthesiology, Instructor, 医学部, 助手 (10345572)
NARITA Minoru  Hoshi University, Pharmaceutical Science, Associate Professor, 薬学部, 助教授 (40318613)
Project Period (FY) 2004 – 2006
Keywordschronic pain / nerve injury / neuropathic pain / anxiety / opioid / amygdala / light-dark test / morphine dependence
Research Abstract

The object of this project is to elucidate the mechanism of neuropathic pain mainly by the action of PKC in the brain and spinal cord, and apply some drugs to chronic pain treatment.
1) Activated PKC in the spinal cord with chronic pain-like hyperalgesia may play a substantial role in the suppression of the morphine-induced rewarding effect with pain-like hyperalgesia. 2) Activation of PKCs (cPKC, PKC ζ) within the spinal cord is directly rewarding effect under a neuropathic pain-like state. 3) The stimulation of spinal PKC results in an enhancement of neuronal activity in the parafascicular nuclei, amygdala and cingulate cortex associated with hyperalgesia. 4) The phosphorylation of the μ-opioid receptor in the spinal cord under a neuropathic pain-like state may contribute to the reduction of in the antinociceptive effect produced by morphine. 5) The mice showed significant anxiety-related behavior with dramatic down-regulations of δ-opioidergic and serotonergic function. 6) Repeated administrations of low-dose antidepressants, imipramine, milnacipran, paroxetine, significantly prevented the anxiety-related behaviors induced by chronic neuropathic pain.
Serotonergic antidepressants are effective for treating anxiety associated with chronic neuropathic pain and useful for treating neuropathic pain with emotional dysfunction. Furthermore, the mechanism of these serotonergic antidepressants may be associated with a down-regulation of serotonergic function in prefrontal cortex and amygdala.

  • Research Products

    (10 results)

All 2006 2004

All Journal Article (10 results)

  • [Journal Article] Chronic pain induces anxiety with concomitant changes in opioidergic function in the amygdala2006

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

      Neuropsychopharmacology 31

      Pages: 739-750

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chronic pain induces anxiety with concomitant changes in opioidergic function in the amygdala.2006

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

      Neuropsychopharmacology 31

      Pages: 739-750

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of the morphine-induced rewarding effect by direct activation of spinal protein kinase C in mice2004

    • Author(s)
      Oe K, et al.
    • Journal Title

      Psychopharmacology 177

      Pages: 55-60

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Implication of spinal proein kinase C in the suppression of morphine-induced rewarding effect under a neuropathic pain-like state in mice2004

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

      Neuroscience 125

      Pages: 545-551

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction of c-fos expression in the mouse brain associated with hyperalgesia induced by intrathecal injection of protein kainease C activator2004

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

      Brain Research 1015

      Pages: 189-193

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Increased phosphorylated- μ -opioid receptor immunoreactivity in the mouse spinal cord following sciatic nerve ligation2004

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

      Neuroscience Letters 354

      Pages: 148-152

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibition of the morphine-induced rewarding effect by direct activation of spinal protein kinase C in mice.2004

    • Author(s)
      Oe K, et al.
    • Journal Title

      Psychopharmacology 177

      Pages: 55-60

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Implication of spinal proein kinase C in the suppression of morphine-induced rewarding effect under a neuropathic pain-like state in mice.2004

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

      Neuroscience 125

      Pages: 545-551

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Induction of c-fos expression in the mouse brain associated with hyperalgesia induced by intrathecal injection of protein kainease C activator.2004

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

      Brain Research 1015

      Pages: 189-193

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Increased phosphorylated-μ-opioid receptor immunoreactivity in the mouse spinal cord following sciatic nerve ligation.2004

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

      Neuroscience Letters 354

      Pages: 148-152

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

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Published: 2008-05-27  

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