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Analysis of pain disease model-associated mitochondrial abnormalities in primary sensory neurons

Research Project

Project/Area Number 26460706
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pain science
Research InstitutionKeio University

Principal Investigator

Shibata Mamoru  慶應義塾大学, 医学部(信濃町), 講師 (60286466)

Co-Investigator(Kenkyū-buntansha) 清水 利彦  慶應義塾大学, 医学部(信濃町), 講師 (40265799)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsミトコンドリア / 三叉神経節ニューロン / 片頭痛 / オートファジー / ミトファジー / 皮質拡延性抑制 / TRPV1 / カプサイシン / 神経修復機構 / 三叉神経節 / リソソーム / アナンダマイド / 神経障害性疼痛 / HMGB1 / ミクログリア / Toll-like receptor / 侵害性刺激
Outline of Final Research Achievements

TRPV1 is activated by capsaicin. We applied 10 mM capsaicin-immersed cotton to the whisker pad for up to 6 days. Electron microscopic analysis revealed that there was extensive destruction of mitochondrial internal structure in small-sized trigeminal ganglion (TG) neurons at Day 4. Nevertheless, no discernible structural alterations were not observed in the small-sized TG neurons at Day 6, implying that there was a restorative process that normalized mitochondrial status in TG neurons exposed to repetitive TRPV1 stimulation. We established a PC12 clone stably expressing TRPV1. When exposed to capsaicin, these cells exhibited mitochondrial structural derangements in a dose-dependent manner. There were significantly increased mitophagy-affected mitochondria in capsaicin-treated cells. Our-cell-based assays imply that mitophagy plays an important role in the reparative process of mitochondrial health in capsaicin-treated cells.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (30 results)

All 2017 2016 2015 2014

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 5 results,  Invited: 14 results)

  • [Journal Article] Signaling Pathways Relevant to Nerve Growth Factor-induced Upregulation of Transient Receptor Potential M8 Expression.2017

    • Author(s)
      Kayama Y, Shibata M, Takizawa T, Ibata K, Nakahara J, Shimizu T, Toriumi H, Yuzaki M, Suzuki N.
    • Journal Title

      Neuroscience

      Volume: 367 Pages: 178-188

    • DOI

      10.1016/j.neuroscience.2017.10.037

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible Involvement of Hypotension in Postprandial Headache: A Case Series.2017

    • Author(s)
      Takizawa T, Shibata M, Hiraide T, Seki M, Takahashi S, Suzuki N.
    • Journal Title

      Headache

      Volume: 57 Issue: 9 Pages: 1443-1448

    • DOI

      10.1111/head.13136

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional interactions between transient receptor potential M8 and transient receptor potential V1 in the trigeminal system: Relevance to migraine pathophysiology2017

    • Author(s)
      Kayama Y, Shibata M, Takizawa T, Ibata K, Shimizu T, Ebine T, Toriumi H, Yuzaki M, Suzuki N.
    • Journal Title

      Cephalalgia

      Volume: 38(5) Issue: 5 Pages: 833-845

    • DOI

      10.1177/0333102417712719

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exploring the role of microglia in cortical spreading depression in neurological disease.2017

    • Author(s)
      Shibata M, Suzuki N.
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 37 Issue: 4 Pages: 1182-1191

    • DOI

      10.1177/0271678x17690537

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression.2017

    • Author(s)
      Takizawa T., Shibata M., Kayama Y., Shimizu T., Toriumi H., Ebine T., Unekawa M., Koh A., Yoshimura A., Suzuki N.
    • Journal Title

      J. Cereb. Blood Flow Metab.

      Volume: 37 Issue: 3 Pages: 890-901

    • DOI

      10.1177/0271678x16647398

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adult-onset recurrent painful ophthalmoplegic neuropathy displaying atypical oculomotor nerve gadolinium-enhancement pattern in the orbit and cavernous sinus.2016

    • Author(s)
      Takizawa T, Shibata M*, Fujiwara H, Shimizu T, Momoshima S, Suzuki N.
    • Journal Title

      Cephalalgia

      Volume: 36 Issue: 2 Pages: 199-200

    • DOI

      10.1177/0333102415583987

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] How have animal studies contributed to the development of migraine research?2016

    • Author(s)
      柴田 護
    • Journal Title

      日本頭痛学会誌

      Volume: 43 Pages: 61-64

    • Related Report
      2016 Research-status Report
  • [Journal Article] ミクログリアと皮質拡延性抑制.2016

    • Author(s)
      柴田 護.
    • Journal Title

      Annual Review神経2016

      Volume: - Pages: 63-68

    • Related Report
      2015 Research-status Report
    • Open Access
  • [Journal Article] Temporal Profiles of HMGB1 Expression Levels after Cortical Spreading Depression in Mice2015

    • Author(s)
      Takizawa T, Shibata M, Kayama Y, Toriumi H, Ebine T, Koh A, Shimizu T, Suzuki N
    • Journal Title

      Cephalalgia

      Volume: 印刷中 Issue: 1 Pages: 44-52

    • DOI

      10.1177/0333102415580100

    • Related Report
      2016 Research-status Report 2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clinical utility of triptans in the management of headache attributed to dural arteriovenous fistula involving the cavernous sinus.2015

    • Author(s)
      39.Osaka M, Shibata M#, Oki K, Yamada S, Kufukibara K, Akiyama T, Yoshida K, Suzuki N. (#corresponding author)
    • Journal Title

      J Neurol Sci

      Volume: 349 Issue: 1-2 Pages: 260-261

    • DOI

      10.1016/j.jns.2015.01.011

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intracranial hemorrhage due to venous thrombosis of developmental venous anomaly during pregnancy.2015

    • Author(s)
      Seki M, Shibata M, Itoh Y, Suzuki N.
    • Journal Title

      J Stroke Cerebrovasc Dis

      Volume: 24

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 専門医部会 シリーズ: 患者の言葉・身体所見を読み解く 頭痛~病歴と画像診断から診断を考える~.2014

    • Author(s)
      柴田 護
    • Journal Title

      日本内科学会雑誌

      Volume: 103 Pages: 2841-2844

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] 薬剤の使用過多による頭痛 (薬物乱用頭痛, MOH)の病態生理と診断.2014

    • Author(s)
      柴田 護
    • Journal Title

      神経内科

      Volume: 81 Pages: 417-422

    • Related Report
      2014 Research-status Report
  • [Presentation] Facial TRPM8 stimulation ameliorates thermal hyperalgesia in a mouse migraine model.2017

    • Author(s)
      Kayama S, Shibata M, Takizawa T, Shimizu T, Toriumi H, Ebine T, Suzuki N.
    • Organizer
      IHC2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cortical spreading depression alters the progranulin expression in cortical neurons.2017

    • Author(s)
      Kitagawa S, Takizawa T, Kayama Y, Toriumi H, Shimizu T, Shibata M, Suzuki N.
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Animal models of migraine: Trigeminovascular system.2017

    • Author(s)
      Shibata M
    • Organizer
      第45回日本頭痛学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 頭痛の病態に関わるHotな分子たち. PACAPとCGRP.2017

    • Author(s)
      Shibata M
    • Organizer
      第45回日本頭痛学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 片頭痛治療のすべて 病態から見た新しい治療の展望. 片頭痛の新しい治療薬.2017

    • Author(s)
      柴田 護
    • Organizer
      第35回日本神経治療学会総会.
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Symposium 3: New therapeutic horizons for migraine. Introduction to novel migraine therapies on the horizon.2016

    • Author(s)
      Shibata M.
    • Organizer
      第44回日本頭痛学会総会
    • Place of Presentation
      Westin都ホテル京都 (京都府京都市)
    • Year and Date
      2016-10-22
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] HMGB1 is an important mediator of multiple CSD-induced microalial activation in the cerebral cortex.2016

    • Author(s)
      Shibata M.
    • Organizer
      The 6th Asian Regional Conference for Headache
    • Place of Presentation
      Seoul (South Korea)
    • Year and Date
      2016-10-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Temporal profiles of TRPM8 and TRPV1 expression in the trigeminal ganglion neurons after CFA-induced inflammation.2016

    • Author(s)
      Kayama Y, Shibata M, Takizawa T, Shimizu T, Toriumi H, Ebine T, Suzuki N.
    • Organizer
      EHMTIC2016
    • Place of Presentation
      Glasgow (Scotland)
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] なおる神経内科「片頭痛の現在・過去・未来」CGRP拮抗薬.2016

    • Author(s)
      柴田 護.
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸国際会議場 (兵庫県神戸市)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 慢性片頭痛と反復性片頭痛はどう違うか?2015

    • Author(s)
      柴田 護.
    • Organizer
      第43回日本頭痛学会総会
    • Place of Presentation
      京王プラザホテル (東京新宿区)
    • Year and Date
      2015-11-14
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] How have animal studoes contributed to the elucidation of migraine pathophysiology?2015

    • Author(s)
      Shibata M.
    • Organizer
      第43回日本頭痛学会総会
    • Place of Presentation
      京王プラザホテル (東京新宿区)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Mechanism of cortical microglial activation after cortical spreading depression.2015

    • Author(s)
      Shibata M.
    • Organizer
      Pan-Asian/Pan-American Program, AHS57th Annual Scientific Meeting.
    • Place of Presentation
      Grand Hyatt Washington, Washington DC. (USA)
    • Year and Date
      2015-06-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 片頭痛の新たな主役たち 片頭痛慢性化2014

    • Author(s)
      柴田 護
    • Organizer
      第42回日本頭痛学会総会
    • Place of Presentation
      山口県下関市海峡メッセ
    • Year and Date
      2014-11-14
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 片頭痛の病態生理2014

    • Author(s)
      柴田 護
    • Organizer
      Headache Master School Japan Tokyo
    • Place of Presentation
      東京 都市センター
    • Year and Date
      2014-09-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] TACsの治療2014

    • Author(s)
      柴田 護
    • Organizer
      Headache Master School Japan Osaka
    • Place of Presentation
      大阪 吉本ビル
    • Year and Date
      2014-07-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 頭痛のanatomy2014

    • Author(s)
      柴田 護
    • Organizer
      Headache Master School Japan Osaka
    • Place of Presentation
      大阪 吉本ビル
    • Year and Date
      2014-07-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Differential cellular localization of antioxidant enzymes in the trigeminal ganglion.2014

    • Author(s)
      Shibata M, Sato H, Shimizu T, Shibata S, Toriumi H, Ebine T, Kuroi T, Iwashita T, Funakubo M, Kayama Y, Akazawa C, Wajima K, Nakagawa T, Okano H, Suzuki N.
    • Organizer
      Pan-Asian/Pan-American Program, American Headache Society 2014, June 2014, Los Angeles.
    • Place of Presentation
      Hyatt Regency Century Plaza, Los Angeles, USA
    • Year and Date
      2014-06-26
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2019-03-29  

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