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Positive emotions and enriched environment reduce pain through the epigenetic modifications in the central nervous system

Research Project

Project/Area Number 24390151
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Pain science
Research InstitutionWakayama Medical University

Principal Investigator

SENBA Emiko  和歌山県立医科大学, 医学部, 博士研究員 (00135691)

Co-Investigator(Kenkyū-buntansha) NARITA Minoru  星薬科大学, 薬学部, 教授 (40318613)
MURAKAMI Kazuo  公益財団法人国際科学振興財団, その他部局等, その他 (70110517)
HORI Miyo  公益財団法人国際科学振興財団, その他部局等, 研究員 (90399329)
Co-Investigator(Renkei-kenkyūsha) KAMI Kstsuya  和歌山県立医科大学, 医学部, 博士研究員 (20204612)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords陽性情動 / マイクロアレイ / 扁桃体 / α-受容体 / 神経障害性疼痛 / 運動療法 / エピジェネティクス / 睡眠障害 / α受容体 / microRNA / エピジェネティクス修飾 / 脳報酬系 / 超音波発声 / 慢性疼痛 / DNAメチル化
Outline of Final Research Achievements

The microarray technique revealed that many genes were up- and down-regulated, especially in amygdala after 4 weeks of tickling stimulation. For example, arufa-adrenergic receptor gene and miR-375-3p were changed in the amygdala of isolated rats, while those in tickled rats were restored, indicating that positive emotions elicited by tickling can reduce stress responses. Treadmill running for 5 days after the partial sciatic nerve ligation significantly improved pain behaviors of neuropathic pain model mice. We revealed that epigenetic mechanisms such as acetylation of H3K9 in activated microglia in the dorsal horn are involved in the exercise-induced hypoalgesia. To clarify the role of VTA dopaminergic neurons on pain threshold, we performed an optogenetic assay by injecting AAV-channelrhodopsin-2 into the VTA of cre-tyrosine hydrolase mice. We found that brain reward system plays a role in the regulation of pain threshold in pathological conditions, such as neuropathic pain state.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (40 results)

All 2015 2014 2013 2012

All Journal Article (15 results) (of which Peer Reviewed: 11 results,  Open Access: 6 results) Presentation (25 results) (of which Invited: 16 results)

  • [Journal Article] A key to dissect the triad of insomnia, chronic pain, and depression.2015

    • Author(s)
      Emiko Senba
    • Journal Title

      Neurosci Lett.

      Volume: 589 Pages: 197-199

    • DOI

      10.1016/j.neulet.2015.01.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible involvement of activated locus coeruleus-noradrenergic neurons in pain-related sleep disorders.2015

    • Author(s)
      Koh K, Hamada A, Hamada Y, Yanase M, Sakaki M, Someya K, Narita M, Kuzumaki N, Ikegami D, Sakai H, Iseki M, Inada E, Narita M.
    • Journal Title

      Neurosci Lett.

      Volume: 589 Pages: 200-6

    • DOI

      10.1016/j.neulet.2014.12.002

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic mechanisms of chronic pain.2015

    • Author(s)
      Descalzi G, Ikegami D, Ushijima T, Nestler EJ, Zachariou V, Narita M.
    • Journal Title

      Trends Neurosci.

      Volume: 38(4) Issue: 4 Pages: 237-246

    • DOI

      10.1016/j.tins.2015.02.001

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuropathic pain-like stimuli change the expression of ribosomal proteins in the amygdala: genome-wide search for a “pain-associated anxiety-related factor2015

    • Author(s)
      Saisu H, Igarashi K, Narita M, Ikegami D, Kuzumaki N, Wajima K, Nakagawa T, Narita M.
    • Journal Title

      Jpn. J. Pharm. Palliat. Care Sci

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 神経障害性疼痛モデルマウスの一次知覚伝達系におけるマクロファージ/ミクログリアの由来と極性化2014

    • Author(s)
      仙波恵美子, 上 勝也
    • Journal Title

      脳21

      Volume: 17

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 神経障害性疼痛に対する運動療法の効果とそのメカニズム2014

    • Author(s)
      上 勝也, 仙波恵美子
    • Journal Title

      ペインクリニック

      Volume: 35 Pages: 1007-1017

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Astrocytic activation in the anterior cingulate cortex is critical for sleep disorder under neuropathic pain.2014

    • Author(s)
      Yamashita A, Hamada A, Suhara Y, Kawabe R, Yanase M, Kuzumaki N, Narita M, Matsui R, Okano H, Narita M.
    • Journal Title

      Synapse

      Volume: 68 Issue: 6 Pages: 235-247

    • DOI

      10.1002/syn.21733

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tickling during adolescence alters fear-related and cognitive behaviors in rats after prolonged isolation2014

    • Author(s)
      Hori M, Yamada K, Ohnishi J, Sakamoto S, Hiroki Furuie, Murakami K, Ichitani Y
    • Journal Title

      Physiol Behav

      Volume: 131 Pages: 62-7

    • DOI

      10.1016/j.physbeh.2014.04.008

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic transcriptional activation of monocyte chemotactic protein 3 contributes to long-lasting neuropathic pain.2013

    • Author(s)
      Imai S, Ikegami D, Yamashita A, Shimizu T, Narita M, Niikura K, Furuya M, Kobayashi Y, Miyashita K, Okutsu D, Kato A, Nakamura A, Araki A, Omi K, Nakamura M, James Okano H, Okano H, Ando T, Takeshima H, Ushijima T, Kuzumaki N, Suzuki T, Narita M.
    • Journal Title

      Brain

      Volume: 136 Issue: 3 Pages: 828-843

    • DOI

      10.1093/brain/aws330

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of sleep disorders under pain using an optogenetic tool: possible involvement of the activation of dorsal raphe nucleus-serotonergic neurons.2013

    • Author(s)
      Ito H, Yanase M, Yamashita A, Kitabatake C, Hamada A, Suhara Y, Narita M, Ikegami D, Sakai H, Yamazaki M, Narita M.
    • Journal Title

      Mol Brain

      Volume: 6 Issue: 1 Pages: 59-59

    • DOI

      10.1186/1756-6606-6-59

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tickling increases dopamine release in the nucleus accumbens and 50 kHz ultrasonic vocalizations in adolescent rats2013

    • Author(s)
      Hori M, Shimoju R, Tokunaga R, Ohkubo M, Miyabe S, Ohnishi J, Murakami K, Kurosawa M.
    • Journal Title

      Neuroreport

      Volume: 24(5) Issue: 5 Pages: 241-245

    • DOI

      10.1097/wnr.0b013e32835edbfa

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Torigoe K, Mori T, Shibasaki M, Yoshizawa K, Narita M, Suzuki T2012

    • Author(s)
      Olanzapine suppresses the rewarding and discriminative stimulus effects induced by morphine.
    • Journal Title

      Synapse

      Volume: 66 Issue: 2 Pages: 174-179

    • DOI

      10.1002/syn.21500

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Usefulness of olanzapine as an adjunct to opioid treatment and for the treatment of neuropathic pain.2012

    • Author(s)
      Torigoe K, Nakahara K, Rahmadi M et al.
    • Journal Title

      Anesthesiology

      Volume: 116 Issue: 1 Pages: 159-169

    • DOI

      10.1097/aln.0b013e31823c7e56

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 痛みの細胞記憶とエピジェネティクス制御2012

    • Author(s)
      成田年、他
    • Journal Title

      Anesthesia 21 Century

      Volume: 14 Pages: 2876-2883

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 老化および脳高次機能疾患におけるエピジェネティクス制御2012

    • Author(s)
      池上大悟、他
    • Journal Title

      日本神経精神薬理学雑誌

      Volume: 32 Pages: 275-280

    • Related Report
      2012 Annual Research Report
  • [Presentation] 難治性疼痛発現機序探索のための“痛みネットワーク”解析に連動した複合型オミクス解析:ケミカルジェネティクスシステムやゲノムワイド解析の応用2015

    • Author(s)
      成田 年
    • Organizer
      第88 回日本薬理学会年会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 離乳後の快情動形成の役割-ラット遊びモデルでの検証.2014

    • Author(s)
      堀美代
    • Organizer
      第216回つくばブレインサイエンス(TBSA)セミナー
    • Place of Presentation
      筑波大学,つくば市
    • Year and Date
      2014-12-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Tickling alters fear-related and cognitive behaviors in rats isolated during adolescence.2014

    • Author(s)
      Hori M, Yamada K, Ohnishi J, Furuie H, Murakami K, Ichitani Y.
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      Washington Convention Center, 米国
    • Year and Date
      2014-11-05 – 2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] エピジェネティクス修飾異常に伴う”痛みの細胞記憶”の形成2014

    • Author(s)
      成田 年
    • Organizer
      第9回臨床ストレス応答学会大会
    • Place of Presentation
      岡山市
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Exercise-induced hypoalgesiaに対する脊髄後角GABA作動性ニューロンの関与2014

    • Author(s)
      上 勝也, 田口 聖, 仙波恵美子
    • Organizer
      第7回日本運動器疼痛学会
    • Place of Presentation
      山口市
    • Year and Date
      2014-10-25 – 2014-10-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Running exercise attenuates neuropathic pain through epinegenetic regulation in spinal microglia.2014

    • Author(s)
      Emiko Senba, Satoru Taguchi, Katsuya Kami:
    • Organizer
      IASP 15th World Congress on Pain
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2014-10-06 – 2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pain-induced epigenetic cell modification and significance of primary pain-control2014

    • Author(s)
      Minoru Narita
    • Organizer
      IASP 15th World Congress on Pain
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2014-10-06 – 2014-10-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 痛みに対する脳の応答:痛みに抵抗する脳.2014

    • Author(s)
      仙波恵美子
    • Organizer
      第8回緩和医療薬学会年会
    • Place of Presentation
      松山市
    • Year and Date
      2014-10-04 – 2014-10-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 慢性痛に対する運動療法奏功のメカニズムと創薬2014

    • Author(s)
      仙波恵美子, 上 勝也
    • Organizer
      第36回線維筋痛症学会
    • Place of Presentation
      長野市
    • Year and Date
      2014-09-13 – 2014-09-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 神経障害性疼痛に対する走運動の効果 ―脊髄後角ミクログリアにおけるヒストンアセチル化の関与―2014

    • Author(s)
      上 勝也, 田口 聖, 仙波恵美子
    • Organizer
      第36回 日本疼痛学会
    • Place of Presentation
      大阪市
    • Year and Date
      2014-06-20 – 2014-06-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 疼痛分子神経科学領域の次世代型研究の提案2014

    • Author(s)
      成田 年
    • Organizer
      第36回日本疼痛学会
    • Place of Presentation
      大阪市
    • Year and Date
      2014-06-20 – 2014-06-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 神経障害時のマクロファージ・ミクログリアの挙動と運動負荷による影響.2014

    • Author(s)
      仙波恵美子
    • Organizer
      第37回 末梢神経を語る会
    • Place of Presentation
      宜野湾市
    • Year and Date
      2014-04-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 神経障害性疼痛に対する走運動の効果 ―脊髄後角ミクログリアにおけるヒストンアセチル化の関与―2014

    • Author(s)
      上 勝也、田口 聖、仙波恵美子
    • Organizer
      第36回 日本疼痛学会シンポジウム
    • Place of Presentation
      大阪市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] RUNNING EXERCISE ATTENUATES NEUROPATHIC PAIN THROUGH EPIGENETIC REGULATION IN SPINAL MICROGLIA.2014

    • Author(s)
      Senba E, Taguchi E, Kami K
    • Organizer
      The 15th International Association for the Study of Pain
    • Place of Presentation
      Buenos Aires, Argentine
    • Related Report
      2013 Annual Research Report
  • [Presentation] オプトジェネティクス手法に基づいた中脳辺縁ドパミン神経系の活性化は多様な生理活性を誘導する2014

    • Author(s)
      渡邉 萌, 池上大悟, 山下 哲, 田崎慶彦, 濵田麻美, 成田道子, 青木一教, 成田 年
    • Organizer
      第87回日本薬理学会年会 シンポジウム
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 最先端技術による神経回路網の多次元解析と脳内微小環境構造の可視化;脳疾患の原因解明を目指して2014

    • Author(s)
      成田 年
    • Organizer
      第87回日本薬理学会年会 シンポジウム
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 疼痛分子神経科学領域の次世代型研究の提案2014

    • Author(s)
      成田 年
    • Organizer
      第36回日本疼痛学会 シンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 光遺伝学的手法を用いた疼痛閾値に対する中脳辺縁ドパミン神経の機能解析2014

    • Author(s)
      渡邉 萌、濱田祐輔、山下 哲、成田道子、池上大悟、葛巻直子、山中章弘、成田 年
    • Organizer
      第36回日本疼痛学会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] Activities of dorsal raphe nucleus-serotonergic neurons and locus coeruleus-noradrenergic ones interfere with sleep: Analysis of pain-related sleep disorders using an optogenetic tool2014

    • Author(s)
      Minoru Narita
    • Organizer
      The 15th International Association for the Study of Pain (Plenary Lecture)
    • Place of Presentation
      Buenos Aires, Argentine
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Tickling alters emotional responses in adolescent rats.2013

    • Author(s)
      Hori, M.
    • Organizer
      The 90^<th> annual Meeting of the Physiological Society in Japan
    • Place of Presentation
      Tokyo
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] Exercise training attenuates neuropathic pain by modulating microglial activation2013

    • Author(s)
      Senba E, Taguchi S, Kami K.
    • Organizer
      The 5th Asian Pain Symposium, Okazaki Conference Center, December, 2013
    • Place of Presentation
      生理学研究所、岡崎市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] CHRONIC NOCICEPTIVE STIMULI NEGATIVELY CONTROL THE MESOLIMBIC DOPAMINERGIC TRANSMISSION2013

    • Author(s)
      Narita M, Yamashita A
    • Organizer
      INTERNATIONAL NARCOTICS RESEARCH CONFERENCE (INRC) 2013
    • Place of Presentation
      North QLD Australia
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Epigenetic transcriptional activation of monocyte chemotactic protein 3 in spinal astrocytes by peripheral neuropathy2013

    • Author(s)
      Ikegami D, Imai S, Yamashita A, Narita M, Takeshima H, Ushijima T, Narita M
    • Organizer
      Society for Neuroscience 2013
    • Place of Presentation
      Society for Neuroscience 2013
    • Related Report
      2013 Annual Research Report
  • [Presentation] Enriched environment飼育による脳由来神経栄養因子(BDNF) promoter領域におけるヒストン修飾の変化2012

    • Author(s)
      神田菜摘、他
    • Organizer
      第6回エピジェネティクス研究会年会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Hippocampal epigenetic modification at the brain-derived neurotophic factor gene induced by an enriched environment.2012

    • Author(s)
      Nagasawa, A, et al.
    • Organizer
      International Society for Stem CeU Research (ISSCR) 10th Annual Meeting
    • Place of Presentation
      Yokohama
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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