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The role of epogenetic modulation in the neuropathic pain

Research Project

Project/Area Number 22689043
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Anesthesiology/Resuscitation studies
Research InstitutionOsaka University

Principal Investigator

NAKAE Aya  大阪大学, 医学(系)研究科(研究院), 准教授 (60379170)

Project Period (FY) 2010-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2010: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords遺伝子後修飾 / 神経障害性疼痛 / バイオマーカー / DNA後修飾 / BDNF / 神経障害痛 / 動物モデル / 眼窩下神経絞扼モデル / メチル化 / 大規模シークエンサー / スプライスバリアント / 定量PCR / エピジェネティック / ヒストン修飾 / 神経因性疼痛
Research Abstract

Pain is one of the most uncomfortable feeling to have of humans, but the mechanism is unclear.In this study, we conducted research by focusing on the epigenetic modification. We focused on the unique feature of brain-derived neurotrophic factor(BDNF)gene construction, we performed the mRNA quantification of the various splice variants, methylation analysis of CpG islands of each splice variant, and histone modification. Many CpG islands methylation rates changes were very little but significantly higher in nerve-injured rats than naive, or naive and sham rats. The dendrogram from methylation profiles of some exon's promoter region demonstrated that classification of nerve injured rats and naive controls at the first branch completely matched the condition. These were considered to be strong candidates for biomarkers of neuropathic pain in the future.

Report

(5 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (57 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (9 results) (of which Peer Reviewed: 2 results) Presentation (44 results) (of which Invited: 6 results) Book (4 results)

  • [Journal Article] Antinociceptive effects of mirtazapine, pregabalin, and gabapentin after chronic constriction injury of the infraorbital nerve in rats2014

    • Author(s)
      Nakai K, Nakae A, Hashimoto R, Mashimo T, Hosokawa K
    • Journal Title

      J Oral Facial Pain Headache

      Volume: 28(1) Issue: 1 Pages: 61-7

    • DOI

      10.11607/jop.1105

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serotonin 2C receptor alternative splicing in a spinal cord injury model2013

    • Author(s)
      Nakae A, Nakai K, Tanaka T, Hosokawa K, Mashimo T
    • Journal Title

      Neurosci Lett

      Volume: 532 Pages: 49-54

    • Related Report
      2013 Final Research Report
  • [Journal Article] Serotonin 2C receptor alternative splicing in a rat model of orofacial neuropathic pain2012

    • Author(s)
      Nakae A, Nakai K, Tanaka T, Hosokawa K, Mashimo T
    • Journal Title

      Neuroscience and Medicine

      Volume: 3 Pages: 69-74

    • Related Report
      2013 Final Research Report
  • [Journal Article] Serotonin 2C Receptor Alternative Splicing in a Rat Model of Orofacial Neuropathic Pain2012

    • Author(s)
      Aya Nakae, Kunihiro Nakai, Tatsuya Tanaka, Ko Hosokawa, Takashi Mashimo
    • Journal Title

      Neuroscience & Medicine

      Volume: Vol.3 No1(In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The animal model of spinal cord injury as an experimental pain model2011

    • Author(s)
      Nakae A, Nakai K, Yano K, Hosokawa K, Shibata M, Mashimo T
    • Journal Title

      Journal of Biomedicine and Biotechnology Volume 2011

      Volume: 939023 Pages: 11-11

    • Related Report
      2013 Final Research Report
  • [Journal Article] Pregnancy Does Not Enhance Volatile Anesthetic Sensitivity on the Brain : An Electroencephalographic Analysis Study2010

    • Author(s)
      Ueyama H, Hagihira S, Takashina M, Nakae A, Mashimo T
    • Journal Title

      Anesthesiology

      Volume: 113(3) Pages: 577-84

    • Related Report
      2013 Final Research Report
  • [Journal Article] Recovery of motoneuron and locomotor function after chronic spinal cord injury depends on constitutive activity in 5-HT2C receptors2010

    • Author(s)
      Murray K, Nakae A, Stephens MJ, Rank M, D'Amico J, Harvey P, Li X, Harris L, Ballou EW, Anelli R, Heckman CJ, Mashimo T, Vavrek R, Sanelli L, Gorassini MA, Bennett DJ and Fouad K
    • Journal Title

      Nature Medicine

      Volume: 16(8) Pages: 694-700

    • Related Report
      2013 Final Research Report
  • [Journal Article] 5-HT2C receptor agonists attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain2010

    • Author(s)
      Nakai K, Nakae A, Sosuke Oba, Mashimo T, Ueda K
    • Journal Title

      European J Pain

      Volume: 14(10) Pages: 999-1006

    • Related Report
      2013 Final Research Report
  • [Journal Article] P2X4 receptor expression in a rat model of trigeminal neuropathic pain2010

    • Author(s)
      Nakai K, Nakae A, Oba S, Mashimo T, Ueda K
    • Journal Title

      Neuroreport

      Volume: 21(8) Pages: 559-563

    • Related Report
      2013 Final Research Report
  • [Presentation] Methylation of BDNF genes in rat oro-facial neuropathic pain model ~possible biomarker of neuropathic pain in the future~2013

    • Author(s)
      Nakae A, Nakai K, Tanaka T, Ishida Y, Ishino S, Hosokawa K, Mashimo T, Fujino Y
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego
    • Year and Date
      2013-11-10
    • Related Report
      2013 Final Research Report
  • [Presentation] The atypical antipsychotics attenuate pain-related behavior in a rat model with trigeminal neuropathic pain2013

    • Author(s)
      Nakai K, Nakae A, Hashimoto R, Fujino Y, Hosokawa K
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego
    • Year and Date
      2013-11-10
    • Related Report
      2013 Final Research Report
  • [Presentation] Pain and executive function2013

    • Author(s)
      Aya Nakae
    • Organizer
      International Symposium on Cognitive Neuroscience Robotics
    • Place of Presentation
      Knowledge Theater, Osaka
    • Year and Date
      2013-08-22
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Pain and attention in elderly volunteers2013

    • Author(s)
      Nakae A
    • Organizer
      International Symposium on Cognitive Neuroscience Robotics
    • Place of Presentation
      Paul G. Allen Center for CSE, University of Washington, Seattle
    • Year and Date
      2013-02-01
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Different effect of experimental electrical pain on autonomic nervous system derived from peripheral perfusion index in healthy volunteers2013

    • Author(s)
      Nakae A, Nishimura T, Shibata M, Mashimo T, Fujino Y
    • Organizer
      8th Congress of the European Federation of IASP chapters-PAIN IN EUROPE VIII
    • Place of Presentation
      Florence
    • Related Report
      2013 Final Research Report
  • [Presentation] Antiallodynic effects of intrathecal administration of atypical antipsychotics in rat model with orofacial neuropathic pain2013

    • Author(s)
      Nakai K, Nakae A, Fujino Y, Hosokawa K
    • Organizer
      8th Congress of the European Federation of IASP chapters-PAIN IN EUROPE VIII
    • Place of Presentation
      Florence
    • Related Report
      2013 Final Research Report
  • [Presentation] Epigenetic regulation of BDNF genes in rat orofacial neuropathic pain model2013

    • Author(s)
      Nakae A, Nakai K, Tanaka T, Hosokawa K, Mashimo T
    • Organizer
      Euroanaesthesia 2013
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] Effects of intrathecal administration of atypical antipsychotics in a rat model of trigeminal neuropathic pain2013

    • Author(s)
      Nakai K, Nakae A, Hashimoto R, Mashimo T, Hosokawa K
    • Organizer
      Euroanaesthesia 2013
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] ハイドロコロイド創傷被覆材の疼痛軽減効果における銀含有による抗菌作用の付加効果の検討2013

    • Author(s)
      中井國博, 中江文, 金澤成行, 藤野裕士, 細川亙
    • Organizer
      第22回形成外科基礎学術集会
    • Place of Presentation
      新潟
    • Related Report
      2013 Final Research Report
  • [Presentation] ラット神経障害性顔面疼痛モデルにおける非定型抗精神病薬による疼痛軽減効果の検討2013

    • Author(s)
      中井國博, 中江文, 金澤成行, 藤野裕士, 細川亙
    • Organizer
      第22回形成外科基礎学術集会
    • Place of Presentation
      新潟
    • Related Report
      2013 Final Research Report
  • [Presentation] Methylation of BDNF genes in rat oro-facial neuropathic pain model ~possible biomarker of neuropathic pain in the future~2013

    • Author(s)
      Nakae A, Nakai K, Tanaka T, Ishida Y, Ishino S, Hosokawa K, Mashimo T, Fujino Y
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      SanDiego(アメリカ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Epigenetic regulation of BDNF genes in rat orofacial neuropathic pain model.2013

    • Author(s)
      Nakae A, Nakai K, Tanaka T, Hosokawa K, Mashimo T
    • Organizer
      Euroanaesthesia 2013
    • Place of Presentation
      Barcelona(スペイン)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経障害モデルにおける遺伝子後修飾2013

    • Author(s)
      中江 文
    • Organizer
      日本麻酔科学会第60回学術集会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] 眼窩下神経絞扼モデルにおけるBDNF遺伝子後修飾の役割2013

    • Author(s)
      中江 文
    • Organizer
      ヨーロッパ麻酔学会
    • Place of Presentation
      バルセロナ
    • Related Report
      2012 Annual Research Report
  • [Presentation] 眼窩下神経絞扼モデルにおけるグルタミン酸受容体の関与2012

    • Author(s)
      中井國博, 中江文, 松田健, 坂井靖夫, 高田章好, 眞下節, 矢野健二, 細川亙
    • Organizer
      第21回形成外科基礎学術集会
    • Place of Presentation
      福島
    • Year and Date
      2012-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 眼窩下神経絞扼モデルにおけるGABA 受容体の関与2012

    • Author(s)
      中井國博, 中江文, 松田健, 坂井靖夫, 高田章好, 眞下節, 矢野健二, 細川亙
    • Organizer
      第21回形成外科基礎学術集会
    • Place of Presentation
      福島
    • Year and Date
      2012-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] ラット足底皮膚欠損モデルでの抗菌性ハイドロコロイド被覆剤(バイオヘッシブAg)の疼痛軽減抑制効果2012

    • Author(s)
      中井國博, 中江文, 松田健, 坂井靖夫, 高田章好, 眞下節, 矢野健二, 細川亙
    • Organizer
      第21回形成外科基礎学術集会
    • Place of Presentation
      福島
    • Year and Date
      2012-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Antinociceptive effects of an antibacterial hydrocolloid wound dressing (biohesive) in a rat skin-defect wound model2012

    • Author(s)
      Nakai K, Nakae A, Kanazawa S, Matsuda K, Sakai Y, Shibata M, Mashimo T, Yano K, Hosokawa K
    • Organizer
      4th Congress of the World Union of Wound Healing Societies
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2012-09-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Intrathecal administration of NR2 antagonists attenuates pain-related behavior in a rat model of trigeminal neuropathic pain2012

    • Author(s)
      Nakai K, Nakae A, Mashimo T, Yano K, Hosokawa K
    • Organizer
      14th WORLD CONGRESS ON PAIN2012
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] Methylation of BDNF genes in rat orofacial neuropathic pain model ~possible biomarker of neuropathic pain in the future~2012

    • Author(s)
      Nakae A., Nakai K., Tanaka T., Hosokawa K., Mashimo T
    • Organizer
      Euroanaesthesia 2012
    • Place of Presentation
      Paris
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of the spinal NR2B-containing NMDA receptors in a rat model of trigeminal neuropathic pain2012

    • Author(s)
      Nakai K., Nakae A., Mashimo T., Yano K., Hosokawa K
    • Organizer
      Euroanaesthesia 2012
    • Place of Presentation
      Paris
    • Related Report
      2013 Final Research Report
  • [Presentation] Mechanisms of Pain2012

    • Author(s)
      Nakae A
    • Organizer
      Workshop on Cognitive Neuroscience
    • Place of Presentation
      Roboics
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 神経因性疼痛におけるGABAA 受容体α 5サブユニットのマイクロRNA による制御2012

    • Author(s)
      中江文, 中井國博, 柴田政彦, 眞下節
    • Organizer
      第34回日本疼痛学会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経障害性疼痛モデルにおける遺伝子後修飾の役割2012

    • Author(s)
      中江 文
    • Organizer
      ヨーロッパ麻酔学会
    • Place of Presentation
      パリ
    • Related Report
      2012 Annual Research Report
  • [Presentation] 眼窩下神経絞扼モデルにおけるミルタザピン, ガバペンチン, プレガバリンの疼痛行動抑制効果2011

    • Author(s)
      中井國博, 中江文, 松田健, 坂井靖夫, 高田章好, 眞下節, 矢野健二, 細川亙
    • Organizer
      第20回形成外科基礎学術集会
    • Place of Presentation
      東京
    • Year and Date
      2011-10-07
    • Related Report
      2013 Final Research Report
  • [Presentation] miR-378 and miR 541 inhibit the expression of the GABAA receptor alpha 5 subunit2011

    • Author(s)
      Nakae A, Nakai K, Tanaka T, Ishida Y, Hagihira S, Mashimo T
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington, DC
    • Related Report
      2013 Final Research Report
  • [Presentation] Antiallodynic effects of miltazapine, gabapentin, and pregabalin in a rat model of trigeminal neuropathic pain2011

    • Author(s)
      Nakai K, Nakae A, Mashimo T, Yano K, Hosokawa K
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Pain in patients with schizophrenia- Difference between electrical and heat stimulation2011

    • Author(s)
      Nakae A, Hashimoto R, Sakai N, Hagihira S, Shibata M, Mashimo T
    • Organizer
      Euroanaesthesia 2011
    • Place of Presentation
      Amsterdam, Holland
    • Related Report
      2013 Final Research Report
  • [Presentation] miRNA inhibit GABA α5 receptor expression, which is responsible for cognitive impairment2011

    • Author(s)
      Yoko Ishida, Tatsuya Tanaka, Akiko Mikami, Yamanaka, Aya Nakae, Satoshi Hagihira, Takashi Mashimo
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] 顔面の神経因性疼痛モデルにおけるBDNF スプライスバリアントの発現変化2011

    • Author(s)
      中江文, 中井 博, 田中達哉, 石田葉子, 矢野健二, 細川亙, 眞下節, 柴田 政彦
    • Organizer
      第4回日本運動器疼痛学会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] ラット後肢ホルマリンテストによる疼痛刺激は脳波変化の推移によって観察できる2011

    • Author(s)
      酒井規広, 中井國博, 中江文, 萩平哲, 眞下節
    • Organizer
      日本麻酔科学会第58回学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] サテライトシンポジウム, 痛みのありか~異分野からみた痛みに対する考え方~2011

    • Organizer
      第33回日本疼痛学会
    • Place of Presentation
      愛媛
    • Related Report
      2013 Final Research Report
  • [Presentation] 脊髄損傷動物モデル動物の疼痛研究への応用2011

    • Author(s)
      中江文, 眞下節
    • Organizer
      第33回日本疼痛学会
    • Place of Presentation
      愛媛
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 情動と痛み, コメディカル講演会 : 痛みとアロマ2011

    • Author(s)
      中江文, 眞下節
    • Organizer
      第33回日本疼痛学会
    • Place of Presentation
      愛媛
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] miR-378 and miR 541 inhibit the expression of the GABAA receptor alpha 5 subunit2011

    • Author(s)
      Aya nakae, Kunihiro Nakai, Tatsuya tanaka, Yoko Ishida, Satoshi Hagihira, Takashi Mashimo
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2011 Annual Research Report
  • [Presentation] 顔面の神経因性疼痛モデルにおけるBDNFスプライスバリアントの発現変化2011

    • Author(s)
      中江文、中井國博、田中達哉、石田葉子、矢野健二、細川亙、眞下節、柴田政彦
    • Organizer
      第4回日本運動器疼痛学会
    • Place of Presentation
      大阪
    • Related Report
      2011 Annual Research Report
  • [Presentation] 脊髄損傷動物モデル動物の疼痛研究への応用2011

    • Author(s)
      中江文、眞下節
    • Organizer
      第33回日本疼痛学会
    • Place of Presentation
      愛媛(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] The role of serotonin 2C receptor RNA editing in the spinal cord injury model2010

    • Author(s)
      Nakae A
    • Organizer
      Bielefeld-Osaka Workshop 2010
    • Place of Presentation
      Bielefeld University, Bielefeld, Germany
    • Year and Date
      2010-10-10
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 眼窩下神経絞扼モデルにおけるセロトニン2C 受容体の関与2010

    • Author(s)
      中江文, 中井國博, 酒井規広, 井上隆弥, 上田晃一, 柴田政彦, 眞下節
    • Organizer
      第32回日本疼痛学会
    • Place of Presentation
      京都
    • Year and Date
      2010-07-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Antiallodynic effects of serotonin 2C receptor agonists in a rat model of trigeminal neuropathic pain2010

    • Author(s)
      Nakai K, Nakae A, Oba S, Yano K, Hosokawa T, Mashimo T, Ueda K
    • Organizer
      Neuroscience 2010
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Serotonin 2C receptor RNA editing and alternative splicing in the rat oro-facial neuropathic pain model2010

    • Author(s)
      Nakae A, Nakai K, Tanaka T, Ishida Y, Mikami A, Yoshida M, Shibata M, Ueda K, Mashimo T
    • Organizer
      NeuPIG
    • Place of Presentation
      Athens, Greek
    • Related Report
      2013 Final Research Report
  • [Presentation] 脊髄坐滅モデルにおけるセロトニン2C 受容体選択的スプライシングの関与2010

    • Author(s)
      石田葉子, 田中達哉, 中江文, 中井國博, 三上晶子, 吉田真理, 柴田政彦, 矢野 健二, 細川亙, 眞下節
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] 眼窩下神経絞扼モデルにおけるアドレナリン受容体の関与2010

    • Author(s)
      中井國博, 中江文, 大場創介, 矢野健二, 細川亙, 真下節, 上田晃一
    • Organizer
      第19回形成外科基礎学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Pain Modulation by Negative and Positive Emotional Sounds

    • Author(s)
      Nakae A, Hermann T, Ikeda T, Sakurai T, Adachi T, Ito H, Nishimura T, Shibata M, Osaka M, Mashimo T
    • Organizer
      4th INTERNATIONAL CONGRESS ON NEUROPATHIC PAIN(IASP)
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2013 Final Research Report
  • [Book] "Mechanisms of Pain". Text book "Cognitive Neuroscience of Robotics"2014

    • Author(s)
      Aya Nakae
    • Publisher
      (in press)
    • Related Report
      2013 Final Research Report
  • [Book] Cognitive Neuroscience Robotics2014

    • Author(s)
      Aya Nakae
    • Total Pages
      26
    • Publisher
      Elsevier
    • Related Report
      2013 Annual Research Report
  • [Book] 神経障害性疼痛. E 神経障害性疼痛と遺伝2011

    • Author(s)
      中江 文 (編集 眞下 節)
    • Publisher
      克誠堂出版
    • Related Report
      2013 Final Research Report
  • [Book] 神経障害性疼痛E神経障害性疼痛と遺伝2011

    • Author(s)
      中江文
    • Total Pages
      6
    • Publisher
      克誠堂出版
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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