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Therapy for intractable pain by intrathecal administration of antisense oligonucleotides of neurotrophic factor

Research Project

Project/Area Number 14571438
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionOkayama University

Principal Investigator

YOKOYAMA Masataka  Okayama University, Graduate School of Medicine, Dentistry, & Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20158380)

Co-Investigator(Kenkyū-buntansha) MIZOBUCHI Satoshi  Okayama University, University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (70311800)
ITANO Yoshitaro  Okayama University, Graduate School of Medicine, Dentistry, & Pharmaceutical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (30127542)
ABE Koji  Okayama University, Graduate School of Medicine, Dentistry, & Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20212540)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsNerve growth factor / Antisense RNA oligonucleotide / Intractable pain
Research Abstract

1.We investigated the spatial and temporal patterns of c-Fos protein (Fos) expression in the dorsal horn of the spinal cord caused by plantar incision in the rat and the effects of pretreatment with local anesthetics. Our results indicate that although pretreatment with local anesthetics suppresses Fos expression for several days in the postoperative period, the analgesic effect is observed only for the expected duration of the local anesthetic used.
2.We measured the mRNAs of cyclooxygenase(COX)-2, and trkB receptor in the spinal cord, and also brain-derived neurotrophic factor(BDNF) in the dorsal root ganglion(DRG) after an injection of formalin in the hind paw of a rat with L5 spinal nerve ligation(SNL)-induced neuropathy. We also measured c-fos mRNA expression in the spinal cord to clarify changes in neuronal activities in the central pathways. c-fos study indicates that the decrease in neuronal activities to inflammation pain in the spinal cord after SNL-induced neuropathy may play an important role in changing in the perception of acute pain. Increase in mRNA of BDNF after SNL-induced neuropathy suggests that overexpression of BDNF in the spinal cord could alleviate formalin-induced pain.
3.We established the real-time PCR method to quantify mRNA in the spinal level. Consequently, we became able to quantify a very small amount of neurotrophic factors. Furthermore, we got a technique of in situ hybridization and intrathecal administration of drugs. Antisense RNA of neurotrophic factors can be administered intrathecally in the neuropathic pain model.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (14 results)

All 2004 2003 2002 Other

All Journal Article (13 results) Publications (1 results)

  • [Journal Article] The effects of pretreatment with lidocaine or bupivacaine on the spatial and temporal expression of c-Fos protein in the spinal cord caused by plantar incision in the rat2004

    • Author(s)
      Sun X, Yokoyama M, Mizobuchi M, Kaku R, Nakatsuka H, Takahashi T, Morita K
    • Journal Title

      Anesth Analg 98

      Pages: 1093-1098

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of percutaneous electrical nerve stimulation with transcutaneous electrical nerve stimulation for long-term pain relief in patients with chronic low back pain2004

    • Author(s)
      Yokoyama M, Sun X, Oku S, Taga N, Sato K, Mizobuchi S, Takahashi T, Morita K
    • Journal Title

      Anesth Analg 98

      Pages: 1552-1556

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Improvement of SSPE by intrathecal infusion of α-IFN2004

    • Author(s)
      Kurata T, Matsubara E, Yokoyama M, Nagano I, Shoji M, Abe K
    • Journal Title

      Neurology 63

      Pages: 398-399

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-term effects of octreotide on pituitary giantism : its analgesic action on cluster headache2004

    • Author(s)
      Otsuka F, Mizobuchi S, Ogura T, Sato K, Yokoyama M, Makino H
    • Journal Title

      Endcr J 51

      Pages: 449-452

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effects of pretreatment with lidocaine or bupivacaine on the spatial and temporal expression of c-Fos protein in the spinal cord caused by plantar incision in the rat.2004

    • Author(s)
      Sun X, Yokoyama M, Mizobuchi M, Kaku R, Nakatsuka H, Takahashi T, Morita K.
    • Journal Title

      Anesth Analg 98

      Pages: 1093-1098

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of percutaneous electrical nerve stimulation with transcutaneous electrical nerve stimulation for long-term pain relief in patients with chronic low back pain.2004

    • Author(s)
      Yokoyama M, Sun X, Oku S, Taga N, Sato K, Mizobuchi S, Takahashi T, Morita K.
    • Journal Title

      Anesth Analg 98

      Pages: 1552-1556

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Improvement of SSPE by intrathecal infusion of α-IFN.2004

    • Author(s)
      Kurata T, Matsubara E, Yokoyama M, Nagano I, Shoji M, Abe K.
    • Journal Title

      Neurology 63

      Pages: 398-399

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-term effects of octreotide on pituitary giantism : its analgesic action on cluster headache.2004

    • Author(s)
      Otsuka F, Mizobuchi S, Ogura T, Sato K, Yokoyama M, Makino H.
    • Journal Title

      Endcr J 51

      Pages: 449-452

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effects of pretreatment with lidocaine or bupivacaine on the spatial and temporal expression of c-Fos protein in the spinal cord caused by plantar incision in the rat2004

    • Author(s)
      Sun X
    • Journal Title

      Anesthesia and Analgesia 98

      Pages: 1093-1098

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cimetidine for chronic calcifying tendonitis of the shoulder2003

    • Author(s)
      Yokoyama M, Aono H, Takeda A, Morita K
    • Journal Title

      Reg Anesth Pain Med 28

      Pages: 248-252

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cimetidine for chronic calcifying tendonitis of the shoulder.2003

    • Author(s)
      Yokoyama M, Aono H, Takeda A, Morita K.
    • Journal Title

      Reg Anesth Pain Med 28

      Pages: 248-252

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Total Spinal anesthesia provides transient relief of intractable pain2002

    • Author(s)
      Yokoyama M, Itano Y, Kusume Y, Oe Y, Mizobuchi S, Morita K
    • Journal Title

      Can J Anaesth 49

      Pages: 810-813

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Total spinal anesthesia provides transient relief of intractable pain.2002

    • Author(s)
      Yokoyama M, Itano Y, Kusume Y, Oe Y, Mizobuchi S, Morita K.
    • Journal Title

      Can J Anaesth 49

      Pages: 810-813

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Xiaohui Sun: "The effect of pretreatment with lidocaine or bupivacaine on the spatial and temporal expression of c-Fos protein in the spinal cord caused by plantar incision in the rat"Anesthesia and Analgesia. (In press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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