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A study of GDNF as a therapeutic drug for neuropathic pain

Research Project

Project/Area Number 11672282
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionNippon Medical School

Principal Investigator

SUZUKI Hidenori  Nippon Medical School, Department of Pharmacology, Associate professor, 医学部, 助教授 (30221328)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsnerve growth factor / neuropathic pain / glial cell line-derived neurotrophic factor / allodynia / hyperalgesia / two-site enzyme immunoassay / dorsal root ganglia / chronic constrictive injury / 痛覚過敏 / 坐骨神経 / RNase protection assay / 免疫組織化学 / タキキニン受容体
Research Abstract

Chronic peripheral nerve injury causes plastic changes in primary afferent neurons, including changes in neurotransmitter synthesis and aberrant synaptic formation, possibly resulting in development of neuropathic pain. Two distinct populations of small sensory neurons are dependent in their survival on nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF), respectively. Therefore, expression of these neurotrophic factors after nerve injury might be responsible for the development of neuropathic pain. If so, manipulation of the expression might become one of the therapeutic strategies for intractable neuropathic pain. To explore this possibility we firstly investigated NGF and GDNF expression in the chronic constrictive injury (CCI) model, using two-site enzyme immunoassay (EIA). After allodynia and hyperalgesia were induced in the hind paw pad of the injured side, tissues were removed and subjected to EIA.While GDNF expression was unchanged in the dorsal root ganglia (DRG) of the 4th (L4) and 5th (L5) lumbar segments, NGF expression increased in the L4 and L5 DRG.GDNF and NGF expressions were decreased in the ligature segment of the sciatic nerve in the CCI side, showing impairment of ordinary neurotrophic factor transport from the respectable tissues. These results suggest that aberrant NGF expression occurs in the DRG and that expression imbalance between NGF and GDNF might play some roles in plastic changes in the sensory neurons and resultant manifestation of persistent pain. We are now investigating whether treatment with excess amount of GDNF reduces neuropathic pain.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Konishi,S.: "Molecular mechanism underlying facilitation of cerebellar GABA-mediated transmission following activation of monoaminergic afferent fibers"Biogenic Amines. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagano,M.: "CDK inhibitors suppress apoptosis induced by chemicals and by excessive expression of a cell death gene, reaper, in Drosophila cells"Apoptosis. 5. 543-550 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hase,A.: "Expression of human GFRα-1 (GDNF receptor) at the neuromuscular junction and myelinated nerves."Neurosci.Lett.. 269. 55-57 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki,H.: "Roles of tachykinins in the synaptic mechanisms in the rat amygdala."Brain Res.. 848. A34 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 高橋直樹: "痛覚伝達に関わる一次ニューロンの栄養因子依存性とその発達変化"Clinical Neuroscience. 18. 351 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 鈴木秀典: "アポトーシスと神経栄養因子"脳と発達. 31. 129-134 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shire Konishi: "Molecular mechanism underlying facilitatjon of cerebellar GABA-mediated transmission following activation of monoaminergic afferent fibers"Biogenic amines. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masatoshi Nagano: "CDK inhibitors suppress apoptosis induced by chemicals and by excessive expression of a cell death gene, reaper, in Drosophila cells"Apoptosis. 5. 543-550 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Asako Hase: "Expression of human GFRα-1 (GDNF receptor) at the neuromuscular junction and myelinated nerves."Neurosci.Lett.. 269. 55-57 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hidenori Suzuki: "Roles of tachykinins in the synaptic mechanisms. in the rat amygdala"Brain Res.. 848. A34 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Konishi,S.: "Molecular mechanism underlying facilitation of cerebellar GABA-mediated transmission following activation of monoaminergic afferent fibers"Biogenic Amines. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagano,M.: "H-7-induced apoptosis in the cells of a Drosophila neuronal cell line through affecting unidentified H-7-sensitive substance (s)."Apoptosis. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋直樹: "痛覚伝達に関わる一次ニューロンの栄養因子依存性とその発達変化"Clinical Neuroscience. 18. 351 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hase, A.: "Expression of human GFRα-1(GDNF receptor)at neuromuscular junction and myelinated nerves."Neurosci. Lett.. 269. 55-57 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki, H.: "Roles of tachykinins in the synaptic mechanisms in the rat amygdala."Brain Res.. 848. A34 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鈴木秀典: "アポトーシスと神経栄養因子"脳と発達. 31. 129-134 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 長谷麻子: "ヒト骨格筋における GDNF(グリア細胞株由来神経栄養因子)の発現"脳の科学. 21. 883-886 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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