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Investigation regarding neuropathic orofacial pain using two-photon microscopy in the insular cortex

Research Project

Project/Area Number 16K11491
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionNihon University

Principal Investigator

FUJITA Satoshi  日本大学, 歯学部, 准教授 (00386096)

Co-Investigator(Kenkyū-buntansha) 崔 翼龍  国立研究開発法人理化学研究所, 生命機能科学研究センター, ユニットリーダー (60312229)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords2光子励起顕微鏡 / カルシウム・イメージング / 侵害刺激 / 下歯槽神経切断モデル / 光学計測法 / 膜電位感受性色素 / 異所性疼痛 / イメージング / 体性感覚野 / 温度感覚 / 神経障害性疼痛 / GCaMP6s / カルシウムイメージング / 島皮質 / 疼痛 / 神経科学 / 口腔生理学 / 神経障害
Outline of Final Research Achievements

Nerve injury could be causing neuropathic pain, such as allodynia and hyperalgesia. In this study, we examined the insular cortex in an inferior alveolar nerve transection animal model and observed responses to electrical stimulation of the dental pulps which primarily transmit nociceptive information to the central nervous system. Optical imaging with a voltage-sensitive dye in the insular cortex revealed enhanced excitatory propagation at the macroscopic level. At the cellular level, calcium imaging using two-photon microscopy revealed enhanced responses in not only excitatory neurons but also inhibitory neurons. These results suggest that plastic changes of the local circuits of the cerebral cortex including the insular cortex might contribute to the enhancement.

Academic Significance and Societal Importance of the Research Achievements

神経障害はアロディニアや痛覚過敏等を誘発することが知られている。本研究では、下歯槽神経切断モデルでは疼痛の処理に関わる島皮質で、侵害刺激を受けた時の興奮伝播が、実際に増大していることが明らかとなった。また、その根底にあるメカニズムとして、単に大脳皮質で興奮性ニューロンの活動性が上がっているだけでなく、神経活動を抑制するはずの抑制性ニューロンの活動性も上がっていることが観察された。これらのことは、神経活動を抑制する機構を含めて何らかの可塑的変化が島皮質を含む大脳皮質の局所回路で起こっていることを示しており、今後、治療ターゲット候補となる可能性が考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

  • [Journal Article] Trigeminal nerve transection-induced neuroplastic changes in the somatosensory and insular cortices in a rat ectopic pain model2019

    • Author(s)
      Fujita S, Yamamoto K, Kobayashi M
    • Journal Title

      eNeuro

      Volume: 6 Issue: 1 Pages: ENEURO.0462-18.2019

    • DOI

      10.1523/eneuro.0462-18.2019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Menthol-induced facilitation of cerebrocortical excitatory propagation induced by air puff stimulation of the nasal cavity in the rat: An optical imaging study2018

    • Author(s)
      Fujita S, Zama M, Kaneko K, Murayama S, Ohtani S, Usui M, Noma D, Tsuda H, Yamamoto K, Kobayashi M
    • Journal Title

      Neurosci Lett

      Volume: 696 Pages: 87-92

    • DOI

      10.1016/j.neulet.2018.12.018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between the fluorescence intensity of rhodamine-labeled orexin A and the calcium responses in cortical neurons: An in?vivo two-photon calcium imaging study2018

    • Author(s)
      Ohtani Saori、Fujita Satoshi、Hasegawa Koki、Tsuda Hiromasa、Tonogi Morio、Kobayashi Masayuki
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 138 Issue: 1 Pages: 76-82

    • DOI

      10.1016/j.jphs.2018.09.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Experimental tooth movement temporally changes neural excitation and topographical map in rat somatosensory cortex2018

    • Author(s)
      Kaneko M, Fujita S, Shimizu N, Motoyoshi M, Kobayashi M
    • Journal Title

      Brain Res

      Volume: 1698 Pages: 62-69

    • DOI

      10.1016/j.brainres.2018.06.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Somatotopic Organization and Temporal Characteristics of Cerebrocortical Excitation in Response to Nasal Mucosa Stimulation With and Without an Odor in the Rat: An Optical Imaging Study2018

    • Author(s)
      Zama Manabu、Hara Yaeko、Fujita Satoshi、Kaneko Tadayoshi、Kobayashi Masayuki
    • Journal Title

      Neuroscience

      Volume: 377 Pages: 77-86

    • DOI

      10.1016/j.neuroscience.2018.02.042

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phase-dependent activity of neurons in the rostral part of the thalamic reticular nucleus with saccharin intake in a cue-guided lever-manipulation task2017

    • Author(s)
      Aoki Ryuhei、Kato Risako、Fujita Satoshi、Shimada Jun、Koshikawa Noriaki、Kobayashi Masayuki
    • Journal Title

      Brain Res

      Volume: 1658 Pages: 42-50

    • DOI

      10.1016/j.brainres.2017.01.013

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 異所性異常疼痛モデルラットにおける大脳皮質の侵害刺激受容応答の亢進2019

    • Author(s)
      藤田 智史、山本 清文、小林 真之
    • Organizer
      第92回薬理学会年会 次世代の会シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] メントールは鼻腔空気圧刺激による大脳皮質応答を増強する2018

    • Author(s)
      坐間学、小林真之、藤田智史、外木守雄
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Enhancement of responses to upper molar pulp stimulation in somatosensory and insular cortices in an ectopic pain model of the rat2018

    • Author(s)
      Satoshi Fujita, Kiyofumi Yamamoto, Masayuki Kobayashi
    • Organizer
      Oral Neuroscience 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] メントールは鼻腔空気圧刺激に対する大脳皮質応答を増強する2018

    • Author(s)
      藤田智史、坐間学、小林真之
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Correlation between fluorescent intensity of rhodamine-labeled orexin and calcium responses of neurons in the insular cortex2017

    • Author(s)
      Ohtani S, Fujita S, Kobayashi M, Hasegawa K, Tonogi M
    • Organizer
      The 11th Sleep Respiration Forum in Hawaii combined with Hawaii Sleep Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 蛍光標識ペプチドの集積を利用した受容体と細胞応答の相関解明に向けた新規アプローチ2017

    • Author(s)
      大谷紗織,藤田智史,外木守雄,小林真之
    • Organizer
      第69回日本大学歯学会総会・学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ラット皮質における咬筋筋紡錘刺激に応答する興奮伝播の時空間的特徴2017

    • Author(s)
      藤田智史,小林真之
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Rhodamine標識オレキシンの蛍光強度とニューロンのカルシウム応答との相関2017

    • Author(s)
      大谷紗織,藤田智史,小林真之,長谷川功紀,外木守雄
    • Organizer
      第16回日本睡眠歯科学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ローダミン標識オレキシンを用いた島皮質ニューロンの受容体数とカルシウム応答の相関の解析2017

    • Author(s)
      藤田智史,小林真之
    • Organizer
      第11回三叉神経領域の感覚―運動統合機構研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Changes of neural activity responding to dental pulp stimulation in an inferior alveolar nerve transection model2016

    • Author(s)
      Satoshi Fujita, Risako Kato, Hiroko Nakamura, Mari Kaneko, Masayuki Kobayashi
    • Organizer
      International Congress on Orofacial Pain
    • Place of Presentation
      Kanagawa Dental Association Hall (Naka-ku, Yokohama)
    • Year and Date
      2016-09-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 歯科薬理学/薬理学HPはこちら - 日本大学歯学部

    • URL

      http://www2.dent.nihon-u.ac.jp/pharmacology/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 日本大学歯学部薬理学講座

    • URL

      http://www2.dent.nihon-u.ac.jp/pharmacology/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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