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Involvement of the 2-Arachidonoylglycerol(2-AG) in attenuation of neuropathic pain

Research Project

Project/Area Number 17H06693
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionNiigata University

Principal Investigator

Kamimura Rantaro  新潟大学, 医歯学総合病院, 医員 (00804535)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords内因性カンナビノイド / 神経障害性疼痛 / 三叉神経 / 生理学
Outline of Final Research Achievements

Exogenous cannabinoids are effective in the attenuation of neuropathic pain. However, since they have side effects, targeting the endocannabinoids (ECs)could represent an alternative approach. The major ECs, 2-arachydonoylglycerol (2-AG) are degraded by monoacylglycerol lipase (MAGL). The head-withdrawal threshold (HWT) was significantly reduced on days 3, 5 and 7, indicating the development of neuropathic pain. We observed that MAGL and Iba-1(microglia marker)immunoreactivity was significantly upregulated in the Vc in neuropathic mice. On day 7, we injected JZL184 at a dose of 4 and 16 mg/kg; the reduced HWT was significantly increased. Two hours after the injection of 16 mg/kg JZL184, the number of immunoreactive cells in the Vc reduced significantly. It is possible that, when the action of MAGL was inhibited by JZL184, the concentration of 2-AG might increase in the brain, including the Vc, and resulted in an attenuation of neuropathic pain.

Academic Significance and Societal Importance of the Research Achievements

内因性カンナビノイド(2-AG)の中枢における鎮痛メカニズムの解明は、神経障害性疼痛の発症機序を明らかにする上で大きな意義がある。しかしながら、内因性カンナビノイド(2-AG)の鎮痛メカニズムにグリア細胞の変化が与える影響は明らかにされていない。したがって、本研究では内因性カンナビノイド(2-AG)による鎮痛メカニズムの解明において、グリア細胞の影響に着目してて解析を進めた。本研究を通して、神経障害性疼痛など難治性の慢性疼痛の病態解明が進み、また内因性カンナビノイド(2-AG)をターゲットとした疼痛治療薬にグリア細胞の抑制機構を組み込むことで新たな疼痛治療薬として報告することができた。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (3 results)

All 2018 2017

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

  • [Journal Article] Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice2018

    • Author(s)
      Kamimura Rantaro、Hossain Mohammad Z.、Unno Shumpei、Ando Hiroshi、Masuda Yuji、Takahashi Kojiro、Otake Masanori、Saito Isao、Kitagawa Junichi
    • Journal Title

      Journal of Oral Science

      Volume: 60 Issue: 1 Pages: 37-44

    • DOI

      10.2334/josnusd.17-0005

    • NAID

      130006539182

    • ISSN
      1343-4934, 1880-4926
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Involvement of the 2-Arachidonoylglycerol(2-AG) in attenuation of neuropathic pain following an injury to the trigeminal nerve in mice2018

    • Author(s)
      Rantaro Kamimura, Kojiro Takahashi, Isao Saito, Kensuke Yamamura
    • Organizer
      The 11th Asian Pacific Orthodontic Conference
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 内因性カンナビノイド分解酵素阻害剤を用いた口腔顔面領域の神経障害性疼痛における鎮痛効果の検討2017

    • Author(s)
      上村 藍太郎, 山村 健介, 齋藤 功
    • Organizer
      第76回日本矯正歯科学会学術大会
    • Related Report
      2017 Annual Research Report

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Published: 2017-08-25   Modified: 2020-03-30  

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