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Elucidation of pain control factors associated with endodontic diseases and construction of an experimental model for pain relief

Research Project

Project/Area Number 21K09911
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Sunakawa Mitsuhiro  東京医科歯科大学, 歯学部, 非常勤講師 (30179288)

Co-Investigator(Kenkyū-buntansha) 興地 隆史  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80204098)
橋本 健太郎  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (80825662)
岡田 大和  東京医科歯科大学, 東京医科歯科大学病院, 医員 (60964921)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords歯髄炎 / 中枢感作 / Kcna1 / Sostdc1 / 視床 / DNAアレイ / RT-rPCR / 疼痛関連遺伝子
Outline of Research at the Start

歯髄炎など歯の疾患の治療後に痛覚過敏などの「病的な痛み」が生じることがあるが、その発症機序には不明な点が多い。本研究は、この種の痛みに対する視床の関与に着目し、ラットに実験的歯髄炎を誘発後、視床に対して網羅的、定量的遺伝子発現解析を行い、歯痛に関与する疼痛制御遺伝子の絞り込みを行う。さらに、これらの因子を上方制御した視床組織を組織培養し、電気刺激に伴う発現挙動の解析から、各疼痛制御遺伝子の役割を解析する

Outline of Final Research Achievements

To elucidate the central sensitization induced by pulpal inflammation and the systemic pain control system, we induced pulpal inflammation by applying allyl-isothiocyanate (mustard oil) to the maxillary molars of rats and comprehensively analyzed gene expression in the thalamus with a DNA array. We revealed that Kcna1 and Sostdc1 gene expression in the thalamus was significantly decreased in the MO-applied group. These findings suggest that loss of function associated with decreased potassium channels and increased BMP signaling may be involved in the central sensitization induced by pulpal inflammation.

Academic Significance and Societal Importance of the Research Achievements

急性歯髄炎の痛みは、我々が感じる痛みの中でもかなり激烈なものであり、中枢感作に関与すると報告されている。しかし、実際にどのように中枢感作を引き起こしているのかについてはいまだ不明な点が多い。今回、ラット上顎臼歯にマスタードオイルを貼付することで、歯髄炎に伴う激しい痛みを誘発した結果、侵害刺激の受容野の一つである視床において、カリウムチャンネルに関与する遺伝子およびBMPのアンタゴニストの発現が低下した。これらのシグナルが歯髄炎の痛みに伴う中枢感作の誘導に関与している可能性が推察されるとともに、これらが中枢性の痛みを制御するターゲットとなりうる可能性が示唆された。

Report

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

    (7 results)

All 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (3 results) Book (1 results)

  • [Journal Article] Hydraulic calcium silicate-based root canal sealers mitigate proinflammatory cytokine synthesis and promote osteogenesis in?vitro2023

    • Author(s)
      Alchawoosh Aseel、Hashimoto Kentaro、Kawashima Nobuyuki、Noda Sonoko、Nozaki Kosuke、Okiji Takashi
    • Journal Title

      Journal of Dental Sciences

      Volume: - Issue: 4 Pages: 1731-1739

    • DOI

      10.1016/j.jds.2022.12.019

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the anti-inflammatory effects of surface-reaction-type pre-reacted glass-ionomer filler containing root canal sealer in lipopolysaccharide-stimulated RAW264.7 macrophages2022

    • Author(s)
      THEIN Htoo Shwe Sin、HASHIMOTO Kentaro、KAWASHIMA Nobuyuki、NODA Sonoko、OKIJI Takashi
    • Journal Title

      Dental Materials Journal

      Volume: 41 Issue: 1 Pages: 150-158

    • DOI

      10.4012/dmj.2021-139

    • NAID

      130008150329

    • ISSN
      0287-4547, 1881-1361
    • Year and Date
      2022-01-25
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulp inflammation induces Kv1.1 K+ channel down-regulation in rat thalamus2022

    • Author(s)
      Murano H, Kaneko T, Zaw SYM, Sone PP, Zaw ZCT, Okada Y, Sunakawa M, Katsube K, Okiji T.
    • Journal Title

      Oral Diseases

      Volume: - Issue: 6 Pages: 1674-1681

    • DOI

      10.1111/odi.13866

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Presentation] ラット臼歯歯髄へのMO貼付に伴う視床におけるSostdc1 mRNA発現の低下2023

    • Author(s)
      岡田大和、川島伸之、野田園子、Nyein Chanko、砂川光宏、興地隆史
    • Organizer
      日本歯科保存学会秋季学術大会(第159回)
    • Related Report
      2023 Annual Research Report
  • [Presentation] Anti-inflammatory effects of hydraulic calcium silicate based endodontic sealers on lipopolysaccharide stimulated macrophages.2022

    • Author(s)
      Alchawoosh A, Hashimoto K, Kawashima N, Okiji T
    • Organizer
      第43回日本歯内療法学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Extracts from hydraulic calcium silicate-based endodontic materials promoted mineralization in murine osteoblastic cells.2022

    • Author(s)
      Alchawoosh A, Hashimoto K, Kawashima N, Nozaki K, Okiji T.
    • Organizer
      日本歯科保存学会 2022年度秋季学術大会(第157回)
    • Related Report
      2022 Research-status Report
  • [Book] エンドドンティクス 第6版2022

    • Author(s)
      興地隆史、川島伸之
    • Total Pages
      284
    • Publisher
      永末書店
    • ISBN
      9784816014048
    • Related Report
      2022 Research-status Report

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

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