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Functional analysis in anterior cingulate cortex and development of therapeutic agent using P2X7 receptor sequences on fibromyalgia

Research Project

Project/Area Number 17K09050
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Migita Keisuke  福岡大学, 薬学部, 教授 (10352262)

Co-Investigator(Kenkyū-buntansha) 松本 太一  福岡大学, 薬学部, 助教 (80570803)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords線維筋痛症 / 疼痛 / 前頭前野 / 帯状回 / ムスカリンM1受容体 / GABAB受容体 / ストレスモデルマウス / 前辺縁皮質 / c-fos / 前帯状回 / P2X7受容体
Outline of Final Research Achievements

We investigated the mechanism of neuropathic pain in the brain of fibromyalgia. To investigate pain assessment and c-fos protein expression, we made mouse models for fibromyalgia, including of RCS (repeated cold stress), SS (social stress), UGIAS (unilateral gastrocnemius injection with acidic saline) and PSNL (partial sciatic nerve ligation) models. All mouse models showed the hypersensitivity to the mechanical stimulation using von Frey filament. In SS and RCS mice, c-fos protein was expressed in prefrontal cortex. On the other hand, PNSL-induced mechanical hypersensitivity was inhibited by an intracerebroventricular administration of a muscarinic M1 receptor agonist. Further, the muscarinic M1 agonist-induced alleviative effect was inhibited by a GABAB receptor antagonist.
These results suggest that the pain in fibromyalgia may be alleviated by a muscarinic M1 receptor agonist and a GABAB receptor agonist.

Academic Significance and Societal Importance of the Research Achievements

線維筋痛症の患者は、日本だけでも200万人はいると推定されており、発症原因は明らかにされていない。また、有効な治療薬がほとんどないため、多くの方が症状の疲労感や疼痛で苦しんでいる。本研究では、慢性疼痛に対して脳内のムスカリンM1受容体アゴニストがGABAB受容体を介して抑制効果があることを示した。今後、中枢性のムスカリンM1受容体アゴニストやGABAB受容体アゴニストを開発することで、線維筋痛症の新たな治療薬を創出できることが期待でき、本研究は学術的および社会的に意義深い。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (16 results)

All 2020 2019 2018 2017 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] Sigma-2 receptor as a potential therapeutic target for treating central nervous system disorders2019

    • Author(s)
      Terada K, Migita K, Matsushima Y, Kamei C
    • Journal Title

      Neural Regen Res

      Volume: 14 Issue: 11 Pages: 1893

    • DOI

      10.4103/1673-5374.259609

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of geldanamycin on neurite outgrowth-related proteins and kinases in nerve growth factor-differentiated pheochromocytoma 12 cells2019

    • Author(s)
      Migita K, Matsumoto T, Terada K, Ono K, Hara S
    • Journal Title

      J Pharmacol Sci

      Volume: 140 Issue: 3 Pages: 255

    • DOI

      10.1016/j.jphs.2019.07.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FF-10501 induces caspase-8-mediated apoptotic and endoplasmic reticulum stress-mediated necrotic cell death in hematological malignant cells2019

    • Author(s)
      Matsumoto T, Jimi S, Migita K, Terada K, Mori M, Takamatsu Y, Suzumiya J, Hara S
    • Journal Title

      Int J Hematol

      Volume: 110 Issue: 5 Pages: 606

    • DOI

      10.1007/s12185-019-02722-x

    • URL

      https://pure.teikyo.jp/en/publications/046d6e1d-8581-4660-97e4-a5bca04890fe

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Muscarinic M<sub>1</sub> receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABA<sub>B</sub> receptors rather than GABA<sub>A</sub> receptors in mice2019

    • Author(s)
      Migita K, Nishimura A, Eto F, Koga K, Matsumoto T, Terada K, Hara S, Honda K.
    • Journal Title

      J Pharmacol Sci.

      Volume: 142 Issue: 2 Pages: 50

    • DOI

      10.1016/j.jphs.2019.06.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stimulating muscarinic M<sub>1</sub> receptors in the anterior cingulate cortex reduces mechanical hypersensitivity via GABAergic transmission in nerve injury rats2019

    • Author(s)
      Koga K, Matsuzaki Y, Migita K, Shimoyama S, Eto F, Nakagawa T, Matsumoto T, Terada K, Mishima K, Furue H, Honda K
    • Journal Title

      Brain Res

      Volume: 1704 Pages: 187

    • DOI

      10.1016/j.brainres.2018.10.013

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GABAB receptor in the antihypersensitive effect in anterior cingulate cortex of partial sciatic nerve ligation model2018

    • Author(s)
      Migita K, Matsuzaki Y, Koga K, Matsumoto T, Mishima K, Hara S, Honda K
    • Journal Title

      J Pharmacological Sciences

      Volume: 137 Issue: 2 Pages: 233-236

    • DOI

      10.1016/j.jphs.2018.05.009

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cholinesterase inhibitor rivastigmine enhances nerve growth factor-induced neurite outgrowth in PC12 cells via sigma-1 and sigma-2 receptors2018

    • Author(s)
      Terada K, Migita K, Matsushima Y, Sugimoto Y, Kamei C, Matsumoto T, Mori M, Matsunaga K, Takata J, Karube Y
    • Journal Title

      PLoS One

      Volume: 13 Issue: 12 Pages: 1-16

    • DOI

      10.1371/journal.pone.0209250

    • URL

      https://pure.teikyo.jp/en/publications/84c8461d-1014-4107-80a5-2f4c89d2bb40

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Propofol anesthesia is reduced in Phospholipase C-related inactive protein type-1 knockout mice2017

    • Author(s)
      Nikaido Y, Furukawa T, Shimoyama S, Yamada J, Migita K, Koga K, Kushikata T, Hirota K, Kanematsu T, Hirata M, Ueno S
    • Journal Title

      The Journal of pharmacology and experimental therapeutics

      Volume: 361(3) Issue: 3 Pages: 367-374

    • DOI

      10.1124/jpet.116.239145

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳内ムスカリンM1受容体はGABAB受容体を介し神経障害性疼痛を抑制する2020

    • Author(s)
      右田啓介、本多健治、松本太一、原周司
    • Organizer
      日本薬学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ボルテゾミブは神経細胞に対して障害作用および突起伸長作用を有する2019

    • Author(s)
      右田啓介、松本太一、原周司
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ボルテゾミブがG-CSFによる造血幹細胞動員を促進するメカニズム2019

    • Author(s)
      松本太一、木村公彦、小野和彦、右田啓介、原周司
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 神経様細胞PC12におけるNGF依存性神経突起伸展作用に対するリバスチグミンの増強機構2018

    • Author(s)
      寺田一樹、松嶋ゆかり、渡瀬大輔、山川博文、松永和久、瀬戸口修一、後藤将太郎、右田啓介、髙田二郎、加留部善晴
    • Organizer
      第48回日本精神神経薬理学会
    • Related Report
      2018 Research-status Report
  • [Presentation] HSP90拮抗薬ゲルダナマイシンにおける神経細胞への影響2018

    • Author(s)
      右田啓介,松本太一,木村公彦,原周司
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] P2X2受容体またはP2X7受容体のNおよびC末部分がもつ機能的特徴2018

    • Author(s)
      右田啓介,松本太一,木村公彦,原周司
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 神経障害性疼痛モデルにおける前帯状回ムスカリン受容体の疼痛抑制とムスカリン受容体発現量2017

    • Author(s)
      本多健治,古賀浩平,松崎雄,右田啓介,中島茂人,牛島悠一,入江圭一,三島健一
    • Organizer
      第70回日本薬理学会西南部会
    • Related Report
      2017 Research-status Report
  • [Remarks] 福岡大学機関リポジトリ薬学集報

    • URL

      https://fukuoka-u.repo.nii.ac.jp/index.php?action=pages_view_main&active_action=repository_view_main_item_snippet&index_id=691&pn=1&count=20&order=7&lang=japanese&page_id=13&block_id=39

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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