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Orofacial pain mechanism due to infant stress

Research Project

Project/Area Number 21K10123
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionNihon University

Principal Investigator

SHIBUTA Ikuko  日本大学, 歯学部, 専修研究員 (60459906)

Co-Investigator(Kenkyū-buntansha) 篠田 雅路  日本大学, 歯学部, 教授 (20362238)
三枝 禎  日本大学, 松戸歯学部, 教授 (50277456)
人見 涼露  日本大学, 歯学部, 講師 (70548924)
林 良憲  日本大学, 歯学部, 准教授 (80582717)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords幼少期ストレス / 一次侵害受容ニューロン / 三叉神経節 / 母子分離ストレス / 頭頸部疼痛 / 衛星細胞
Outline of Research at the Start

幼少期ストレスは,成熟期の感覚神経系にさまざまな機能的変化を引き起こす。幼児期の虐待経験は成熟期に発症する頭頸部筋痛を増悪させることが報告されていることから,幼少期ストレスは頭頸部疼痛伝達系に可塑的変化を引き起こし,成熟期の異常疼痛強度の調節に関与する可能性がある。研究代表者らは,これまでに頭頸部のさまざまな異常疼痛には三叉神経節に存在する衛星細胞や炎症性細胞といった非神経細胞の活性化が重要な役割を果たすことを解明してきた。本研究では, 幼少期ストレス負荷モデル動物を作製し,幼少期ストレスに起因した成熟期に発症する頭頸部疼痛に対する三叉神経節内の活性化衛星細胞の機能的役割を明らかにする。

Outline of Final Research Achievements

The involvement of the Nav1.8 and the CCL2/CCR2 signaling in the trigeminal ganglion (TG) in facial skin incisional pain hypersensitivity was examined. The whisker pad skin was incised on postnatal day 4 and week 7. Mechanical hypersensitivity was enhanced in Incision-Incision group. The number of Nav1.8-immunoreactive TG neurons and the amount of CCL2 expressed in the macrophages and satellite glial cells in the TG were increased on day 14 after re-incision in the Incision-Incision group. Blockages of Nav1.8 and CCR2 suppressed the enhancement of mechanical hypersensitivity in the Incision-Incision group. CCL2 enhanced mechanical hypersensitivity. Our results suggest that neonatal facial injury accelerates the TG neuronal hyperexcitability following orofacial skin injury in adult in association with Nav1.8 overexpression via CCL2 signaling, resulting in the enhancement of orofacial incisional pain hypersensitivity in the adulthood.

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまで注目されてこなかった幼少期ストレス負荷による免疫細胞-侵害受容ニューロン間コミュニケーションの可塑的変化によって発症する頭頸部疼痛の分子基盤を解明したことであり,学術的独自性が高い研究であると確信する。本研究の成果は,幼少期ストレス負荷に起因した成熟期に発症する顎顔面部領域の異常疼痛発症のメカニズム解明に留まらず,臨床応用を念頭においてEBMに基づいた異常疼痛治療に対するターゲット分子の同定に寄与し,新規治療法の創造に繋げることができる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Remarks (1 results)

  • [Journal Article] Involvement of oxidative stress in orofacial mechanical pain hypersensitivity following neonatal maternal separation in rats2023

    • Author(s)
      Soma Chihiro、Hitomi Suzuro、Oshima Eri、Hayashi Yoshinori、Soma Kumi、Shibuta Ikuko、Tsuboi Yoshiyuki、Shirakawa Tetsuo、Kikuiri Takashi、Iwata Koichi、Shinoda Masamichi
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 22760-22760

    • DOI

      10.1038/s41598-023-50116-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neonatal Injury Modulates Incisional Pain Sensitivity in Adulthood: An Animal Study2023

    • Author(s)
      Soma Kumi、Hitomi Suzuro、Hayashi Yoshinori、Soma Chihiro、Otsuji Jo、Shibuta Ikuko、Furukawa Akihiko、Urata Kentaro、Kurisu Ryoko、Yonemoto Mamiko、Hojo Yasushi、Shirakawa Tetsuo、Iwata Koichi、Shinoda Masamichi
    • Journal Title

      Neuroscience

      Volume: 519 Pages: 60-72

    • DOI

      10.1016/j.neuroscience.2023.03.018

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased PPARgamma in the trigeminal spinal subnucleus caudalis due to neonatal injury contributes to incision-induced mechanical allodynia in female rats2022

    • Author(s)
      Otsuji Jo、Hayashi Yoshinori、Hitomi Suzuro、Soma Chihiro、Soma Kumi、Shibuta Ikuko、Iwata Koichi、Shirakawa Tetsuo、Shinoda Masamichi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 19314-19314

    • DOI

      10.1038/s41598-022-23832-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Remarks] 日本大学歯学部生理学講座

    • URL

      http://www2.dent.nihon-u.ac.jp/g.physiology/

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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