Ectopic orofacial pain mechanisms following inferior alveolar injury

• Project/Area Number: 18K09732
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Nihon 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) ; 岩田 幸一 日本大学, 歯学部, 特任教授 (60160115) ; 久保 亜抄子 生理学研究所, 生体機能調節研究領域, 特別協力研究員 (70733202)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 異所性疼痛 / 三叉神経節 / サテライト細胞 / 下歯槽神経損傷

Outline of Final Research Achievements

Ectopic orofacial pain occurs after trigeminal nerve injuries. In this study, we focused the involvement of functional interaction between neuron and satellite glial cells via NO- and TrkC-dependent mechanisms in orofacial ectopic pain with inferior alveolar nerve injury (IANI).
The findings in this study suggest that IANX leads to satellite glial cell activation via NO released from TG neurons. The activation of satellite glial cells spreads to large areas within the TG and can affect uninjured branches of the trigeminal nerve, resulting in orofacial mechanical hypersensitivity not directly associated with the IANI. Moreover, the amount of NT-3 increased in Schwann cells in the injured IAN. The TrkC neutralization inhibited the orofacial mechanosensory disturbance. Therefore, functional interaction between neuronal ganglion and satellite glial cells via NO- and TrkC-dependent mechanisms play an important role in orofacial ectopic pain associated with IANI.

Academic Significance and Societal Importance of the Research Achievements

現在、三叉神経損傷によって口腔顔面領域に引き起こされる異所性疼痛に関しては、対症療法としてリリカを初めとする数種類の薬物が使用されるのみで、サテライト細胞あるいはサテライト細胞間の機能連絡をターゲットとした薬物療法に関しては全く情報が得られていない。本研究は、三叉神経損傷によって口腔顔面領域に発症した異所性の異常疼痛治療に対して、サテライト細胞の結合タンパクあるいはサテライト細胞の活性化阻害薬の臨床応用を視野に入れた新たな臨床研究プロジェクトへとつなげることが可能である。

Research Products

• [Journal Article] Microglial activation in the trigeminal spinal subnucleus interpolaris/caudalis modulates orofacial incisional mechanical pain hypersensitivity associated with orofacial injury in infancy (2021)
  • Author(s): Matsui Tomoyuki、Hitomi Suzuro、Hayashi Yoshinori、Shibuta Ikuko、Otsuji Jo、Ando Masatoshi、Inada Takanobu、Soma Kumi、Iwata Koichi、Shirakawa Tetsuo、Shinoda Masamichi
  • Journal Title: Journal of Oral Science Volume: 63 Issue: 2 Pages: 170-173
  • DOI: 10.2334/josnusd.20-0648
  • NAID: 130008009557
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity (2020)
  • Author(s): Ikutame Daisuke、Urata Kentaro、Oto Tatsuki、Fujiwara Shintaro、Iinuma Toshimitsu、Shibuta Ikuko、Hayashi Yoshinori、Hitomi Suzuro、Iwata Koichi、Shinoda Masamichi
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 21 Pages: 7871-7871
  • DOI: 10.3390/ijms21217871
  • Peer Reviewed
• [Journal Article] Microglia-Astrocyte Communication via C1q Contributes to Orofacial Neuropathic Pain Associated with Infraorbital Nerve Injury (2020)
  • Author(s): Asano Sayaka、Hayashi Yoshinori、Iwata Koichi、Okada-Ogawa Akiko、Hitomi Suzuro、Shibuta Ikuko、Imamura Yoshiki、Shinoda Masamichi
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 18 Pages: 6834-6834
  • DOI: 10.3390/ijms21186834
  • Peer Reviewed / Open Access
• [Journal Article] Oxytocin-dependent regulation of TRPs expression in trigeminal ganglion neurons attenuates orofacial neuropathic pain following intraorbital nerve injury in rats (2020)
  • Author(s): Ando M, Hayashi Y, Hitomi S, Shibuta I, Furukawa A, Oto T, Inada T, Matsui T, Fukaya C, Noma N, Okubo M, Yonehara Y, Kaneko T, Iwata K, Shinoda M
  • Journal Title: Int. J. Mol. Sci. Volume: 21 Issue: 23 Pages: 9173-9190
  • DOI: 10.3390/ijms21239173
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Involvement of Satellite Cell Activation via Nitric Oxide Signaling in Ectopic Orofacial Hypersensitivity (2020)
  • Author(s): Lee Jun、Ohara Kinuyo、Shinoda Masamichi、Hayashi Yoshinori、Kubo Asako、Sugawara Shiori、Asano Sayaka、Soma Kumi、Kanno Kohei、Ando Masatoshi、Koyama Ryo、Kimura Yuki、Sakanashi Kousuke、Iinuma Toshimitsu、Iwata Koichi
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 4 Pages: 1252-1252
  • DOI: 10.3390/ijms21041252
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increase in IGF-1 Expression in the Injured Infraorbital Nerve and Possible Implications for Orofacial Neuropathic Pain (2019)
  • Author(s): Sugawara Shiori、Shinoda Masamichi、Hayashi Yoshinori、Saito Hiroto、Asano Sayaka、Kubo Asako、Shibuta Ikuko、Furukawa Akihiko、Toyofuku Akira、Iwata Koichi
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 24 Pages: 6360-6360
  • DOI: 10.3390/ijms20246360
  • Peer Reviewed / Open Access
• [Presentation] Nitric oxide を介した衛星細胞の活性化は口腔顔面異所疼痛発症に関与する (2018)
  • Author(s): 李 淳, 篠田雅路, 岩田幸一
  • Organizer: 第95回日本生理学会