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Chronic pain treatment strategy targeting PACAP-PAC1-induced astrocyte signaling

Research Project

Project/Area Number 26462384
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionKagoshima University

Principal Investigator

Ohnou Tetsuya  鹿児島大学, 医歯学域附属病院, 助教 (60457661)

Co-Investigator(Kenkyū-buntansha) 栗原 崇  鹿児島大学, 医歯学域医学系, 准教授 (60282745)
宮田 篤郎  鹿児島大学, 医歯学域医学系, 教授 (60183969)
上村 裕一  鹿児島大学, 医歯学域医学系, 教授 (30211189)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsPACAP / PAC1 / アストロサイト / JNK / 慢性痛 / 慢性疼痛 / アロディニア
Outline of Final Research Achievements

Pituitary adenylate cyclase activating polypeptide (PACAP) is present in the spinal dorsal horn and dorsal root ganglia, and markedly upregulated in peripheral nerve injury or inflammation, suggesting an important role in the modulation of spinal nociceptive transmission. However, the involvement of PACAP type 1 (PAC1) receptor and its downstream signaling mechanism have not been clarified yet. We found that a single intrathecal injection of PACAP or maxadilan (a PAC1 receptor agonist) produced long-lasting mechanical allodynia, and the spinal PAC1 receptor stimulation also caused sustained astrocytic activation. Our data suggest that the interaction between dorsal horn neurons and astrocytes evoked by PAC1 receptor-mediated signal transduction is critically involved in the induction and maintenance of the long-lasting mechanical allodynia. The signaling pathway linking between PAC1 receptor stimulation and astroglial activation may offer a new opportunity to treat chronic pain.

Report

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

    (25 results)

All 2017 2016 2015 2014

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (17 results)

  • [Journal Article] Spinal astrocyteic activation contribites to both induction and maintenance of pituitary adenylate cyclase-activating polypeptyde type 1 receptor-induced long-lasting mechanical allodynia in mice2016

    • Author(s)
      Masafumi Yokai, Takashi Kurihara, Atsuro Miyata
    • Journal Title

      Molecular Pain

      Volume: 12 Pages: 1-13

    • DOI

      10.1177/1744806916646383

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide type1 receptor signaling evokes long- lasting nocicetive behaviors through the activation of spinal astrocytes in mice2016

    • Author(s)
      Tetsuya Ohnou, Masafumi Yokai, Takashi Kurihara, Maiko Hasegawa-Moriyama, Takao Shimizu, Kazuhiko Inoue, Yuki Kambe, Yuichi Kanmura, Atsuro Miyata
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 130 Pages: 194-203

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice2015

    • Author(s)
      Kambe, Y, Miyata, A
    • Journal Title

      Neurosci Lett

      Volume: 588 Pages: 166-171

    • DOI

      10.1016/j.neulet.2015.01.006

    • NAID

      130007812003

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.2015

    • Author(s)
      Karki P, Kurihara T, Nakamachi T, Watanabe J, Asada T, Oyoshi T, Shioda S, Yoshimura M, Arita K, Miyata A.
    • Journal Title

      Mol Pain.

      Volume: 11(1) Pages: 6-6

    • DOI

      10.1186/s12990-015-0003-8

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] C-type natriuretic peptide modulates permeability of the blood-brain barrier2014

    • Author(s)
      M. Bohara, Y. Kambe, T. Nagayama, H. Tokimura, K. Arita, and A. Miyata
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 34 Issue: 4 Pages: 589-596

    • DOI

      10.1038/jcbfm.2013.234

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors.2014

    • Author(s)
      Kurihara T, Sakurai E, Toyomoto M, Kii I, Kawamoto D, Asada T, Tanabe T, Yoshimura M, Hagiwara M, Miyata A.
    • Journal Title

      Mol Pain.

      Volume: 10 Pages: 17-17

    • DOI

      10.1186/1744-8069-10-17

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Characterization of Neural-Restrictive Silencer Element in Mouse Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Gene Expression2014

    • Author(s)
      Sugawara H, Tominaga A, Inoue K, Takeda Y, Yamada K, Miyata A
    • Journal Title

      J Mol Neurosci

      Volume: 54 Issue: 3 Pages: 526-534

    • DOI

      10.1007/s12031-014-0348-x

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Perfusion index as a possible predictor for postanesthetic shivering.2014

    • Author(s)
      Kuroki C, Godai K, Hasegawa-Moriyama M, Kuniyoshi T, Matsunaga A, Kanmura Y, Kuwaki T.
    • Journal Title

      J Anesth.

      Volume: 28 Issue: 1 Pages: 19-25

    • DOI

      10.1007/s00540-013-1658-9

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 種々疼痛モデルマウスにおける新規PAC1受容体アンタゴニストの薬理学的評価2017

    • Author(s)
      長島涼太、上田隆拡、渡辺藍、岡田卓哉、栗原崇、宮田篤郎、豊岡尚樹、髙﨑一朗
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎パブリックホール、長崎新聞文化ホール アストピア(長崎県・長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] ニトログリセリン誘発偏頭痛モデルマウスを用いた新規PAC1アンタゴニストの評価2017

    • Author(s)
      柴崎知華、渡辺 藍、栗原 崇、宮田篤郎、豊岡尚樹、髙﨑一朗
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎パブリックホール、長崎新聞文化ホール アストピア(長崎県・長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] PACAP誘導性機械的アロディニアと神経突起伸長におけるBtg2の関与に関する研究2017

    • Author(s)
      加藤翔、宮田篤郎、栗原崇、髙﨑一朗
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎パブリックホール、長崎新聞文化ホール アストピア(長崎県・長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] PACAPシグナリングによって駆動されるアストロサイト‐ニューロン乳酸シャトルの中枢神経機能発現への寄与2017

    • Author(s)
      神戸悠輝、用皆正文、中島 優、新谷 紀人、橋本 均、高﨑 一朗、栗原 崇、宮田 篤郎
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎パブリックホール、長崎新聞文化ホール アストピア(長崎県・長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 難治性疼痛治療を目指した新規PACAP特異的受容体拮抗薬の開発.2017

    • Author(s)
      用皆正文、栗原 崇、渡辺 藍、長島涼太、合田浩明、豊岡尚樹、髙﨑一朗、宮田篤郎
    • Organizer
      第10回 桜ヶ丘地区(基礎系)研究発表会
    • Place of Presentation
      鹿児島大学 鶴陵会館(鹿児島県・鹿児島市)
    • Year and Date
      2017-02-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 難治性疼痛治療を目指したPACAP特異的受容体アンタゴニストの開発2017

    • Author(s)
      髙﨑一朗、渡辺 藍、長島涼太、合田浩明、豊岡尚樹、宮田篤郎、栗原 崇
    • Organizer
      生理研研究会 痛み研究会2016
    • Place of Presentation
      自然科学研究機構岡崎地区(愛知県・岡崎市)
    • Year and Date
      2017-01-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 種々疼痛モデルマウスにおける新規PAC1受容体アンタゴニストの薬理学的評価2016

    • Author(s)
      長島涼太、上田隆拡、渡辺藍、岡田卓哉、栗原崇、宮田篤郎、豊岡尚樹、髙﨑一朗
    • Organizer
      日本薬学会北陸支部第128例会
    • Place of Presentation
      北陸大学 薬学キャンパス(石川県・金沢市)
    • Year and Date
      2016-11-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] PACAP誘発長期機械的アロディニア現象発症におけるCyr61/CCN1の関与2016

    • Author(s)
      栗原 崇、用皆正文、八坂敏一、神戸悠輝、前田辰則、原 博満、高﨑一朗、宮田篤郎
    • Organizer
      第69回日本薬理学会西南部会
    • Place of Presentation
      松山大学(愛媛県・松山市)
    • Year and Date
      2016-11-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] PACAP誘発性長期機械的痛覚過敏における脊髄アストロサイト-ニューロン乳酸シャトルの関与2016

    • Author(s)
      神戸悠輝、栗原 崇、用皆正文、前田辰則、高﨑一朗、宮田篤郎
    • Organizer
      第9回トランスポーター研究会九州部会
    • Place of Presentation
      宮崎市民プラザ(宮崎県・宮崎市)
    • Year and Date
      2016-10-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] Spinal astrocyte activation triggered by PACAP-PAC1 receptor signaling pathway contributes to both induction and maintenance of long-lasting mechanical allodynia.2016

    • Author(s)
      Takashi Kurihara, Masafumi Yokai, Yuki Kambe, Ichiro Takasaki, Atsuro Miyata
    • Organizer
      IASP2016
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Involvement of spinal Cyr61 in PAC1 receptor-mediated long-term mechanical allodynia in mice.2016

    • Author(s)
      Ichiro Takasaki, Tatsunori Maeda, Masafumi Yokai, Atsuro Miyata, Takashi Kurihara
    • Organizer
      IASP2016
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] PACAP誘発性長期機械的アロディニアの発症における脊髄アストロサイト-ニューロン乳酸シャトルの関与2016

    • Author(s)
      神戸悠輝、栗原崇、用皆正文、前田辰則、高﨑一朗、宮田篤郎
    • Organizer
      第13回GPCR研究会
    • Place of Presentation
      日本科学未来館、未来館ホール(東京都)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 培養アストロサイトにおける下垂体アデニル酸シクラーゼ活性化ポリペプチドによるグリコーゲン代謝の活性化2015

    • Author(s)
      神戸悠輝、中島優、新谷紀人、橋本均、宮田篤郎
    • Organizer
      第88回日本薬理学年会
    • Place of Presentation
      名古屋・名古屋国際会議場
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 脊髄におけるPACAP特異的受容体の刺激はアストロサイト活性化を介して長期機械的アロディニア反応を誘発する2015

    • Author(s)
      用皆正文、栗原崇、神戸悠輝、高崎一郎、宮田篤郎
    • Organizer
      第88回日本薬理学年会
    • Place of Presentation
      名古屋・名古屋国際会議場
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 下垂体アデニル酸シクラーゼ活性化ポリペプチドによる脳内グリコーゲン代謝の活性化~培養アストロサイトを用いた研究~2014

    • Author(s)
      神戸悠輝、宮田篤郎
    • Organizer
      第67回日本薬理学会西南部会
    • Place of Presentation
      北九州市・産業医科大学
    • Year and Date
      2014-11-23
    • Related Report
      2014 Research-status Report
  • [Presentation] Spinal PACAP-PAC1-receptor signaling pathway induces long-lasting mechanical allodynia through the activation of astrocytes in mice2014

    • Author(s)
      Youkai M, Kurihara T, Asada T, Kambe Y, Inoue K, Miyata A
    • Organizer
      Society for Neuroscience 2014
    • Place of Presentation
      米国・ワシントン
    • Year and Date
      2014-11-20 – 2014-11-25
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳虚血におけるPAC1遺伝子発現の抑制メカニズム2014

    • Author(s)
      宮田篤郎、三浦綾子、神戸悠輝、辰川英樹、栗原崇、小嶋聡一
    • Organizer
      第11回GPCR研究会
    • Place of Presentation
      東京・日本科学未来館
    • Year and Date
      2014-05-09 – 2014-05-10
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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