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Study of the gene therapy with extracorporeal shockwaves for Discogenic low back pain

Research Project

Project/Area Number 17591547
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionChiba University

Principal Investigator

TAKAHASHI Kazuhisa  Chiba University, Graduate School of Medicine, Assistant Professor, 大学院医学研究院, 助教授 (20179477)

Co-Investigator(Kenkyū-buntansha) OHTORI Seiji  Chiba University, Hospital, Assistant, 医学部附属病院, 助手 (40361430)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsextracorporeal shockwave / Nuclear Factor-kappa Decoy / discogenic low back pain / inflammatory pain / gene therapy / 腰椎椎間板性腰痛 / 椎間板 / 除痛 / 変性
Research Abstract

Study Design. In vitro and in vivo study of a rat inflammatory pain model using nuclear factor-kappa B (NF-kB) decoy.
Summary and Background Data. Transcription factor NF-kB is reported to play a crucial role in regulating proinflammatory cytokine gene expression. We hypothesized that inhibiting NF-kB gene expression with NF-kB decoy may suppress inflammatory pain.
Methods. NF-kB decoy-FITC was induced in explant culture, endoneurally injected into the sciatic nerve, and its transduction efficiency into DRG measured. For behavioral testing, 12 rats received plantar injections of complete Freund's adjuvant and were divided into three groups : decoy group - single endoneural injection of 10111 of NF-kB decoy (n=4) ; saline group - single endoneural injection of 10μl of saline (n=4) ; and naive group - untreated (n=4). Behavioral testing was performed using von Frey filaments and a Hargreaves device with a heat source.
Results. Total transduction efficiency of NF-kB decoy-FITC was 53.6% in vitro and 20.5% in vivo. No statistical differences were observed with respect to types of cell size distributions of all FITC-positive neurons. In behavioral testing, withdrawal latencies or thresholds significantly differed between the decoy group and the saline group from 2 to 14 days after surgery in the mechanical allodynia experiments, and from 2 to 3 days after surgery in the thermal hyperalgesia experiments.
Conclusions. NF-kB decoy was conveyed and transduced into DRG both in vivo and in vitro. Additionally, NF-kB decoy reduced mechanical allodynia and thermal hyperalgesia in the rat inflammatory pain model, suggesting that inhibition of NF-kB with NF-kB decoy may represent a key mechanism for mediating inflammation or reducing inflammatory pain.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (24 results)

All 2006 2005

All Journal Article (24 results)

  • [Journal Article] Substance P-saporin down-regulates substance P receptor immunoreactive sensory dorsal root ganglion neurons innervating the lumbar intervertebral discs in rats.2006

    • Author(s)
      Ohtori S
    • Journal Title

      Spine 31(26)

      Pages: 2987-2991

    • NAID

      10020584936

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Injection of nuclear factor-kappa B decoy into the sciatic nerve suppresses mechanical allodynia and thermal hyperalgesia in a rat inflammatory pain model.2006

    • Author(s)
      Inoue G
    • Journal Title

      Spine 31(25)

      Pages: 2904-2908

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nerve fiber ingrowth into scar tissue formed following nucleus pulposus extrusion in the rabbit anular-puncture disc degeneration model : effects of depth of puncture.2006

    • Author(s)
      Aoki Y
    • Journal Title

      Spine 31(21)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of acid-sensing ion channel 3 in dorsal root ganglion neurons following application of nucleus pulposus on nerve root in rats.2006

    • Author(s)
      Ohtori S
    • Journal Title

      Spine 31(18)

      Pages: 2048-2052

    • NAID

      10020589423

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Exposure of the nucleus pulposus to the outside of the anulus fibrosus induces nerve injury and regeneration of the afferent fibers innervating the lumbar intervertebraldiscs in rats.2006

    • Author(s)
      Inoue G
    • Journal Title

      Spine 31(13)

      Pages: 1433-1438

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Extracorporeal Shockwaves induce the expression of ATF3 and GAP-43 in rat dorsal root ganglion neurons.2006

    • Author(s)
      Murata R
    • Journal Title

      Auton Neurosci 128(1-2)

      Pages: 96-100

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Substance P-saporin down-regulates substance P receptor immunoreactive sensory dorsal root ganglion neurons innervating the lumbar intervertebral discs in rats.2006

    • Author(s)
      Ohtori S, Inoue G, Koshi T, Ito T, Doya H, Moriya H, Takahashi K.
    • Journal Title

      Spine. 31(26)

      Pages: 2987-2991

    • NAID

      10020584936

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Injection of nuclear factor-kappa B decoy into the sciatic nerve suppresses mechanical allodynia and thermal hyperalgesia in a rat inflammatory pain model.2006

    • Author(s)
      Inoue G, Ochiai N, Ohtori S, Nakagawa K, Gemba T, Doya H, Ito T, Koshi T, Moriya H, Takahashi K.
    • Journal Title

      Spine. 31(25)

      Pages: 2904-2908

    • NAID

      10020585475

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nerve fiber ingrowth into scar tissue formed following nucleus pulposus extrusion in the rabbit anular-puncture disc degeneration model : effects of depth of puncture.2006

    • Author(s)
      Aoki Y, Akeda K, An H, Muchleman C, Takahashi K, Moriya H, Masuda K.
    • Journal Title

      Spine. 31(21)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of acid-sensing ion channel 3 in dorsal root ganglion neurons following application of nucleus pulposus on nerve root in rats.2006

    • Author(s)
      Ohtori S, Inoue G, Koshi T, Ito T, Doya H, Saito T, Moriya H, Takahashi K.
    • Journal Title

      Spine. 31(18)

      Pages: 2048-2052

    • NAID

      10020589423

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Exposure of the nucleus pulposus to the outside of the anulus fibrosus induces nerve injury and regeneration of the afferent fibers innervating the lumbar intervertebral discs in rats.2006

    • Author(s)
      Inoue G, Ohtori S, Aoki Y, Ozawa T, Doya H, Saito T, Ito T, Akazawa T, Moriya H, Takahashi K.
    • Journal Title

      Spine. 31(13)

      Pages: 1433-1438

    • NAID

      10020592611

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Extracorporeal shockwaves induce the expression of ATF3 and GAP-43 in rat dorsal root ganglion neurons.2006

    • Author(s)
      Murata R, Ohtori S, Ochiai N, Takahashi N, Saisu T, Moriya H, Takahashi K, Wada Y.
    • Journal Title

      Auton Neurosci. 128(1-2)

      Pages: 96-100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Substance P-saporin down-regulates substance P receptor immunoreactive sensory dorsal root ganglion neurons innervationg the lumbar intervertebral discs in rats.2006

    • Author(s)
      Ohtori S
    • Journal Title

      Spine. 31(26)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Injection of nuclear factor-kappa B decoy into the sciatic nerve suppresses mechanical allodynia and thermal hyperalgesia in a rat inflammatory pain model.2006

    • Author(s)
      Inoue g
    • Journal Title

      Spine. 31(25)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nerve fiber ingrowth into scar tissue formed following nucleus pulposus extrusion in the rabbit anular-puncture disc degeneration model : effects of depth of puncture.2006

    • Author(s)
      Aoki Y
    • Journal Title

      Spine. 31(21)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Up-regulation of acid-sensing ion channel 3 indorsal root ganglion neurons following application of nucleus pulposus on nerve root in rats.2006

    • Author(s)
      Ohtori S
    • Journal Title

      Spine. 31(18)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Exposure of the nucleus pulposus to the outside of the anulus fibrosus induces nerve injury and regeneration of the afferent fibers innervating the lumbar intervertevraldiscs in rats.2006

    • Author(s)
      Inoue G
    • Journal Title

      Spine. 31(13)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] extracorporeal shockwaves induce the expression of ATF3 and GAP-43 in rat dorsal root ganglion neurons.2006

    • Author(s)
      Murata R
    • Journal Title

      Auton Neurosci. 128(1-2)

      Pages: 96-100

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Extracellular signal-regulated kinase mitogen-activated protein kinase activation in the dorsal root ganglion (DRG) and spinal cord after DRG injury in rats.2005

    • Author(s)
      Doya H
    • Journal Title

      Spine 30.20

      Pages: 2252-2256

    • Related Report
      2005 Annual Research Report
  • [Journal Article] c-Jun N-terminal kinase activation in dorsal root ganglion contributes to pain hypersensitivity.2005

    • Author(s)
      Doya H
    • Journal Title

      Biochem Biophys Res Commun. 335.1

      Pages: 132-138

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression and co-expression of VR1, CGRP, and IB4-binding glycoprotein in dorsal root ganglion neurons in rats : differences between the disc afferents and the cutaneous afferents.2005

    • Author(s)
      Aoki Y
    • Journal Title

      Spine 30.13

      Pages: 1496-1500

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Insertional torque of the lumbar pedicle screw during surgery.2005

    • Author(s)
      Ozawa T
    • Journal Title

      J Orthop Sci 10.2

      Pages: 133-136

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Change of dorsal horn neurochemistry in a mouse model of neuropathic cancer pain.2005

    • Author(s)
      Shimoyama M
    • Journal Title

      Pain 114.1.2

      Pages: 221-230

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Characteristics of sensory DRG neurons innervating the lumbar facet joints in rats.2005

    • Author(s)
      Ishikawa T
    • Journal Title

      Eur Spine J 14.6

      Pages: 559-564

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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