Elucidation of the onset mechanism of orofacial pain with the aim of establishing a new treatment for toothache

• Project/Area Number: 16K11566
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Conservative dentistry
• Research Institution: Nihon University
• Principal Investigator: SHIMIZU Kohei 日本大学, 歯学部, 准教授 (10508609)
• Co-Investigator(Kenkyū-buntansha): 篠田 雅路 日本大学, 歯学部, 准教授 (20362238) ; 本田 訓也 日本大学, 歯学部, ポスト・ドクトラル・フェロー (20548945)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 関連痛 / 歯痛 / 歯髄炎 / 歯痛錯誤 / 非歯原性歯痛 / 異所性疼痛 / 筋痛 / 関連通 / Hyperalgesia / Allodynia / IL-1β / TRPV1 / Connexin43 / 口腔顔面痛 / 歯内治療学 / 診査診断

Outline of Final Research Achievements

The onset of pulpitis induces excitability enhancement of orofacial skin, adjacent dental pulp and paired dental pulp. It was clarified that activation and enhanced expression of Connexin 43, Satellite glial cells, TRPV1, IL-1β, IL-1 RI, etc. in the trigeminal ganglia are involved as the factors. In addition, it was revealed that the contraction duration of the masseter muscle induces the enhanced expression and activation of pERK and astrocytes in the trigeminal spinal nucleus and contributes to the ectopic hyperalgesia enhancement of the dental pulp.

Academic Significance and Societal Importance of the Research Achievements

この発症メカニズムの本態を解明することは、診査・診断法の精度そのものが向上するだけでなく、新たな治療法の確立も可能となり、極めて臨床的意義および患者貢献度の高いプロジェクトであるといえる。また患者の通院期間の短縮は結果として国の医療費削減にも寄与し、本研究推進による経済的影響も大きいと考えられる。

Research Products

• [Journal Article] Connexin 43 expression in satellite glial cells contributes to ectopic tooth-pulp pain (2018)
  • Author(s): Komiya Hiroki、Shimizu Kohei、Ishii Kae、Kudo Hiroshi、Okamura Teinosuke、Kanno Kohei、Shinoda Masamichi、Ogiso Bunnai、Iwata Koichi
  • Journal Title: Journal of Oral Science Volume: 60 Issue: 4 Pages: 493-499
  • DOI: 10.2334/josnusd.17-0452
  • NAID: 130007553060
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of transient receptor potential vanilloid 1 channel expression in orofacial cutaneous hypersensitivity following tooth pulp inflammation (2018)
  • Author(s): Watase Tetsuro、Shimizu Kohei、Komiya Hiroki、Ohara Kinuyo、Iwata Koichi、Ogiso Bunnai
  • Journal Title: Journal of Oral Science Volume: 60 Issue: 1 Pages: 8-13
  • DOI: 10.2334/josnusd.16-0854
  • NAID: 130006539183
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] Role of medullary astroglial glutamine synthesis in tooth pulp hypersensitivity associated with frequent masseter muscle contraction (2018)
  • Author(s): Watase Tetsuro、Shimizu Kohei、Ohara Kinuyo、Komiya Hiroki、Kanno Kohei、Hatori Keisuke、Noma Noboru、Honda Kuniya、Tsuboi Yoshiyuki、Katagiri Ayano、Shinoda Masamichi、Ogiso Bunnai、Iwata Koichi
  • Journal Title: Mol pain Volume: 14 Pages: 1-11
  • DOI: 10.1177/1744806918763270
  • Peer Reviewed / Open Access
• [Journal Article] Role of Neuron-Glial Interaction Mediated by IL-1β in Ectopic Tooth Pain (2017)
  • Author(s): Komiya H.、Shimizu K.、Noma N.、Tsuboi Y.、Honda K.、Kanno K.、Ohara K.、Shinoda M.、Ogiso B.、Iwata K.
  • Journal Title: J Dent Res Volume: 97 Issue: 4 Pages: 467-475
  • DOI: 10.1177/0022034517741253
  • Peer Reviewed
• [Journal Article] Sensitization of TRPV1 and TRPA1 via peripheral mGluR5 signaling contributes to thermal and mechanical hypersensitivity (2017)
  • Author(s): Honda Kuniya、Shinoda Masamichi、Kondo Masahiro、Shimizu Kohei、Yonemoto Hisashi、Otsuki Katsuhiko、Akasaka Ryuta、Furukawa Akihiko、Iwata Koichi
  • Journal Title: Pain Volume: 158 Issue: 9 Pages: 1754-1764
  • DOI: 10.1097/j.pain.0000000000000973
  • Peer Reviewed / Open Access
• [Journal Article] Cracked tooth syndrome mimicking trigeminal autonomic cephalalgia: A report of four cases. (2017)
  • Author(s): Noma N, Shimizu K, Watanabe K, Young A, Imamura Y, Khan J
  • Journal Title: Quintessence Int Volume: 48 Pages: 329-337
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Bactericidal effect of hydroxyl radicals generated by the sonolysis and photolysis of hydrogen peroxide for endodontic applications (2017)
  • Author(s): Ibi H, Hayashi M, Yoshino F, Tamura M, Yoshida A, Kobayashi Y, Shimizu K, Lee M-C, Imai K, Ogiso B
  • Journal Title: Microbial Pathogenesis Volume: 103 Pages: 65-70
  • DOI: 10.1016/j.micpath.2016.12.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Botulinum neurotoxin type A alleviates mechanical hypersensitivity associated with infraorbital nerve constriction injury in rats. (2017)
  • Author(s): Noma N, Watanabe K, Sato Y, Imamura Y, Yamamoto Y, Ito R, Maruno M, Shimizu K, Iwata K.
  • Journal Title: Neurosci Lett. Volume: 623 Pages: 96-101
  • DOI: 10.1016/j.neulet.2016.11.043
  • Peer Reviewed
• [Presentation] 咬筋痛に関与した歯髄痛覚過敏発症の神経機構解明 (2017)
  • Author(s): 清水康平，渡瀬哲郎，小木曾文内
  • Organizer: 日本歯科保存学会秋季学術大会
• [Presentation] 急性歯髄炎により誘導される歯痛錯誤の末梢神経機構 (2017)
  • Author(s): 古宮宏記，清水康平，大原絹代，高橋なつみ，小木曾文内
  • Organizer: 第146回度日本歯科保存学会秋季学術大会
• [Presentation] 無髄神経欠損モデルラットにおける島皮質局所回路の変化 (2016)
  • Author(s): 村山 翔太, 武市 収, 清水 康平, 小林 真之, 小木曾 文内
  • Organizer: 第145回度日本歯科保存学会秋季学術大会
  • Place of Presentation: キッセイ文化ホール（長野県松本市）
• [Presentation] 急性歯髄炎により誘導される歯痛錯誤の末梢神経機構 (2016)
  • Author(s): 古宮 宏記，清水 康平，渡瀬 哲郎，篠田 雅路，岩田 幸一，小木曾 文内
  • Organizer: 第21回日本口腔顔面痛学会学術大会
  • Place of Presentation: 神奈川県歯科医師会館（神奈川県横浜市）
• [Presentation] 咬筋痛に誘発される歯髄痛覚過敏へのアストロサイトの関与 (2016)
  • Author(s): 渡瀬 哲郎，清水 康平，篠田 雅路，古宮 宏記，岩田 幸一,小木曾 文内
  • Organizer: 第21回日本口腔顔面痛学会学術大会
  • Place of Presentation: 神奈川県歯科医師会館（神奈川県横浜市）
• [Book] 抜髄 Initial Treatment 治癒に導くための歯髄への臨床アプローチ (2016)
  • Author(s): 興地 隆史, 新井 恭子, 小木曾 文内, 佐藤 勧哉, 大島 勇人, 松浦 信幸, 泉 英之, 北村 和夫, 澁川 義幸, 長谷川 誠実, 阿部 修, 吉川 剛正, 田崎 雅和, 清水 康平, 加藤 広之, 田中 利典, 村松 敬, 羽鳥 啓介, 澤田 則宏, 石井 宏, 五十嵐 勝, 大原 絹代, 佐藤 暢也, 清水 花織, 北島 佳代子, 篠田 雅路, 岩波 洋一
  • Total Pages: 400
  • Publisher: 株式会社ヒョーロン・パブリッシャーズ