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Pathogenesis of neuropathic pain due to interaction between peripheral and central sensitization

Research Project

Project/Area Number 16K08994
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pain science
Research InstitutionWakayama Medical University

Principal Investigator

Kiguchi Norikazu  和歌山県立医科大学, 医学部, 講師 (90433341)

Co-Investigator(Kenkyū-buntansha) 岸岡 史郎  和歌山県立医科大学, 医学部, 教授 (60137255)
雑賀 史浩  和歌山県立医科大学, 医学部, 助教 (10644099)
Research Collaborator MATSUZAKI Shinsuke  
KOBAYASHI Daichi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経障害性疼痛 / アロディニア / マクロファージ / 神経炎症 / ミクログリア / サイトカイン / 坐骨神経 / 脊髄後角 / 末梢感作 / 2型糖尿病 / ニコチン受容体 / ケモカイン / 脊髄 / 中枢感作 / ニューロペプチド
Outline of Final Research Achievements

Peripheral sensitization due to inflammatory macrophages play a key role in the pathogenesis of neuropathic pain. In this study, we found that inhibition of peripheral macrophages decreased in the expression of pain-related molecules in the dorsal root ganglion, and it prevented the activation of microglia in the spinal cord after nerve injury. Moreover, such peripheral sensitization caused by macrophages was observed in diabetes-associated neuropathic pain. Collectively, interaction between peripheral and central sensitization might be a common mechanism underlying different types of neuropathic pain.

Academic Significance and Societal Importance of the Research Achievements

神経系の傷害などによって生じる神経障害性疼痛は従来の鎮痛薬に抵抗性であり、その分子基盤に基づいた新しい治療戦略が必要とされている。これまでのげっ歯類を用いた検討では、末梢性感作と中枢性感作はそれぞれ独立して検討されていた。本研究では、末梢性感作が中枢性感作を直接的に制御することを明らかにした点、さらにそのような末梢性感作が異なる病態モデル間で共通して重要であることを明らかにして点に学術的意義がある。さらに新しい創薬標的を示唆していることから、社会的意義も大きいと言える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (22 results)

All 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Wake Forest University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Wake Forest University(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Wake Forest University(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Inflammatory Macrophages in the Sciatic Nerves Facilitate Neuropathic Pain Associated with Type 2 Diabetes Mellitus.2019

    • Author(s)
      Saika F, Kiguchi N, Matsuzaki S, Kobayashi D, Kishioka S.
    • Journal Title

      J Pharmacol Exp Ther.

      Volume: 368(3) Issue: 3 Pages: 535-544

    • DOI

      10.1124/jpet.118.252668

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential mRNA expression of neuroinflammatory modulators in the spinal cord and thalamus of type 2 diabetic monkeys.2018

    • Author(s)
      Ding H, Kiguchi N, Kishioka S, Ma T, Peters CM, Ko MC.
    • Journal Title

      J Diabetes

      Volume: 10(11) Issue: 11 Pages: 886-895

    • DOI

      10.1111/1753-0407.12780

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates.2018

    • Author(s)
      Ding H, Kiguchi N, Yasuda D, Daga PR, Polgar WE, Lu JJ, Czoty PW, Kishioka S, Zaveri NT, Ko MC.
    • Journal Title

      Sci Transl Med

      Volume: 10(456) Issue: 456

    • DOI

      10.1126/scitranslmed.aar3483

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inhibition of peripheral macrophages by nicotinic acetylcholine receptor agonists suppresses spinal microglial activation and neuropathic pain in mice with peripheral nerve injury2018

    • Author(s)
      Kiguchi N, Kobayashi D, Saika F, Matsuzaki S, Kishioka S
    • Journal Title

      J Neuroinflammation

      Volume: 15 Issue: 1 Pages: 96-96

    • DOI

      10.1186/s12974-018-1133-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages2017

    • Author(s)
      Kiguchi N, Kobayashi D, Saika F, Matsuzaki S, Kishioka S
    • Journal Title

      Int J Mol Sci

      Volume: 18 Issue: 11 Pages: 2296-2296

    • DOI

      10.3390/ijms18112296

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peripheral administration of interleukin-13 reverses inflammatory macrophage and tactile allodynia in mice with partial sciatic nerve ligation2017

    • Author(s)
      Kiguchi N, Sakaguchi H, Kadowaki Y, Saika F, Fukazawa Y, Matsuzaki S, Kishioka S
    • Journal Title

      J Pharmacol Sci

      Volume: 133 Issue: 1 Pages: 53-56

    • DOI

      10.1016/j.jphs.2016.11.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Altered expression of glial markers, chemokines, and opioid receptors in the spinal cord of type 2 diabetic monkeys2017

    • Author(s)
      Kiguchi N, Ding H, Peters CM, Kock ND, Kishioka S, Cline JM, Wagner JD, Ko MC
    • Journal Title

      Biochim Biophys Acta

      Volume: 1863 Issue: 1 Pages: 274-283

    • DOI

      10.1016/j.bbadis.2016.10.007

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Inflammatory macrophages mediate neuropathic pain caused by type 2 diabetes mellitus.2018

    • Author(s)
      Kiguchi N, Saika F, Kobayashi D, Matsuzaki S, Kishioka S.
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inflammatory macrophages in the injured peripheral nerves facilitate spinal microglial activation and neuropathic pain in mice.2018

    • Author(s)
      Kiguchi N, Saika F, Kobayashi D, Matsuzaki S, Kishioka S.
    • Organizer
      17th World Congress on Pain
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] α4β2 ニコチン性アセチルコリン受容体アゴニストはマウスにおける2型糖尿病性神経障害性疼痛を減弱する.2018

    • Author(s)
      雑賀史浩, 木口倫一, 小林大地, 松﨑伸介, 岸岡史郎.
    • Organizer
      第40回日本疼痛学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 炎症性マクロファージは神経傷害後のミクログリア活性化および機械的アロディニアを調節する.2018

    • Author(s)
      木口倫一, 雑賀史浩, 小林大地, 松﨑伸介, 岸岡史郎.
    • Organizer
      第40回日本疼痛学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経障害性疼痛モデルマウスを用いた抗炎症性マクロファージの機能解析.2018

    • Author(s)
      小林大地, 木口倫一, 雑賀史浩, 松﨑伸介, 岸岡史郎.
    • Organizer
      第38回鎮痛薬・オピオイドペプチドシンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非ヒト霊長類における疼痛制御因子の発現と機能解析.2018

    • Author(s)
      木口倫一, 岸岡史郎, Mei-Chuan Ko.
    • Organizer
      第38回鎮痛薬・オピオイドペプチドシンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経障害性疼痛に関与するマクロファージ/ミクログリアの機能解析.2018

    • Author(s)
      雑賀史浩, 木口倫一, 小林大地, 松﨑伸介, 岸岡史郎.
    • Organizer
      第134回日本薬理学会近畿部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マクロファージ上で発現するα4β2ニコチン性アセチルコリン受容体活性化による神経障害性疼痛の緩和2017

    • Author(s)
      雑賀史浩、木口倫一、松﨑伸介、岸岡史郎
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 2型糖尿病発症カニクイザルの脊髄後角におけるケモカイン発現変動2017

    • Author(s)
      木口倫一、Huiping Ding、雑賀史浩、松﨑伸介、岸岡史郎、Mei-Chuan Ko
    • Organizer
      生理学研究所研究会「痛みの理解を目指した先端的アプローチ」
    • Place of Presentation
      岡崎
    • Year and Date
      2017-01-31
    • Related Report
      2016 Research-status Report
  • [Presentation] ニコチン性アセチルコリン受容体リガンドの末梢投与は神経障害性疼痛を改善する2017

    • Author(s)
      木口倫一、雑賀史浩、松﨑伸介、岸岡史郎
    • Organizer
      第5回ニューロカンファレンス和歌山
    • Place of Presentation
      和歌山
    • Year and Date
      2017-01-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 傷害神経に浸潤するマクロファージは脊髄ミクログリアの活性化を調節する2017

    • Author(s)
      木口倫一、雑賀史浩、小林大地、松﨑伸介、岸岡史郎
    • Organizer
      第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 神経傷害後の末梢マクロファージによる脊髄ミクログリア調節作用2017

    • Author(s)
      木口倫一、小林大地、雑賀史浩、松﨑伸介、岸岡史郎
    • Organizer
      第131回日本薬理学会近畿部会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-21  

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