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Mechanisms of dysfunction of locus coeruleus in chronic neuropathic pain model

Research Project

Project/Area Number 16K20080
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Anesthesiology
Research InstitutionGunma University

Principal Investigator

Suto Takashi  群馬大学, 大学院医学系研究科, 助教 (60739621)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords青斑核 / 神経障害性疼痛 / 脳由来神経栄養因子 / 内因性鎮痛 / 慢性痛 / ノルアドレナリン
Outline of Final Research Achievements

This study focused on the balance of excitatory/inhibitory neurotransmitter in the locus coeruleus in order to examine the functional change of locus coeruleus following peripheral nerve injury (SNL model). The balance was assessed by measuring the concentration of glutamate and GABA with in vivo microdialysis. At 6 weeks following nerve injury, the animals did not show pain induced analgesia that reflects a part of endogenous analgesia. In the locus coeruleus of the animals, glutamate did not increase even after painful stimulation. Five days repeated treatment with 7,8-dihydroxyflavone (BDNF receptor agonist) could reverse the dysfuction of locus coeruleus by decreasing GABA release after painful stimulation. The restoration resulted in enhancement of analgesic effect of pregabalin. Co-administration of 7,8-dihydroxyflavone with pregabalin could be a novel strategy to treat chronic neuropathic pain.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2017 2016

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] 神経栄養因子シグナルは神経障害性疼痛モデルにおける下行性疼痛抑制系の減弱を回復させる2017

    • Author(s)
      須藤貴史、太田浄、斎藤繁
    • Organizer
      日本麻酔科学会第64回学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 慢性期神経障害性疼痛モデルにおける内因性鎮痛機構の減弱と急性痛の遷延化におけるノルアドレナリンを介した下行性抑制系の役割2017

    • Author(s)
      須藤貴史、太田浄、加藤大樹、斎藤繁
    • Organizer
      第39回日本疼痛学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effects of Brain-derived Neurotrophic Factor Signals on the Noradrenergic Descending Pain Inhibitory Systems2016

    • Author(s)
      Takashi Suto
    • Organizer
      16th World Congress on Pain
    • Place of Presentation
      横浜
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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