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Investigation for the histamine-related mechanism of neuropathic pain and development of its therapy

Research Project

Project/Area Number 25460725
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SAKURADA Shinobu  東北薬科大学, 薬学部, 教授 (30075816)

Co-Investigator(Kenkyū-buntansha) MIZOGUCHI Hirokazu  東北薬科大学, 薬学部, 准教授 (30360069)
WATANABE Chizuko  東北薬科大学, 薬学部, 講師 (90296020)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsヒスタミン / 難治性疼痛 / 脊髄 / ポリアミン / NMDA受容体 / 掻痒
Outline of Final Research Achievements

On the state of neuropathic pain, histamine-evoked pain-sensation, which is mediated through the direct activation of polyamine-recognition site of NMDA receptor in spinal cord by histamine, is enhanced. On the other hand, the super-sensitivity of TRPV1 receptor on the planter skin of paw was revealed to induce the neuropathic pain. The results of this project suggest that the spinal polyamine-recognition site of NMDA receptor and TRPV1 receptor on the skin may be key targets to develop the new therapy for neuropathic pain.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (42 results)

All 2016 2015 2014 2013 Other

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results) Presentation (29 results) Book (2 results)

  • [Journal Article] Intrathecal morphine-3-glucuronide-induced nociceptive behavior via δ-2 opioid receptors in the spinal cord2016

    • Author(s)
      Takaaki Komatsu, Soh Katsuyama, Hiroshi Nagase, Hirokazu Mizoguchi, Chikai Sakurada, Minoru Tsuzuki, Shinobu Sakurada, Tsukasa Sakurada
    • Journal Title

      Pharmacology Biochemistry & Behavior

      Volume: 140 Pages: 68-74

    • DOI

      10.1016/j.pbb.2015.10.010

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Involvement of spinal glutamate in nociceptive behavior induced by intrathecal administration of hemokinin-1 in mice2016

    • Author(s)
      Chizuko Watanabe, Hirokazu Mizoguchi, Giacinto Bagetta, Shinobu Sakurada
    • Journal Title

      Neuroscience Letters

      Volume: 617 Pages: 236-239

    • DOI

      10.1016/j.neulet.2016.02.027

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ラベンダーオイルの末梢局所皮下投与によるパクリタキセル誘発性末梢神経障害性疼痛抑制効果の検討2016

    • Author(s)
      勝山壮、音羽亮、武井佐和子、櫻田忍、倉本敬二
    • Journal Title

      日本未病システム学会雑誌

      Volume: 22 Pages: 47-53

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of RXR/PPARγ underlies neuroprotection by bexarotene in ischemic stroke2015

    • Author(s)
      Michelangelo Certo, Yasuyuki Endo, Kiminori Ohta, Shinobu Sakurada, Giacinto Bagetta, Diana Amantea
    • Journal Title

      Pharmacological Research

      Volume: 102 Pages: 298-307

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Spinal ERK2 activation through δ2-opioid receptors contributes to nociceptive behavior induced by intrathecal injection of leucine-enkephalin2014

    • Author(s)
      Takaaki Komatsu, Soh Katsuyama, Hirokazu Mizoguchi, Chikai Sakurada, Minoru Tsuzuki, Shinobu Sakurada, Tsukasa Sakurada
    • Journal Title

      Peptides

      Volume: 54 Pages: 131-139

    • DOI

      10.1016/j.peptides.2014.01.014

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of multipleμ-opioid receptor subtypes on the presynaptic or postsynaptic inhibition of spinal pain transmission2014

    • Author(s)
      Hirokazu Mizoguchi, Hirokazu Takagi, Chizuko Watanabe, Akihiko Yonezawa, Takumi Sato, Tsukasa Sakurada, Shinobu Sakurada
    • Journal Title

      Peptides

      Volume: 51 Pages: 15-25

    • DOI

      10.1016/j.peptides.2013.10.012

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differential alternation of the antinociceptive effect of narcotic analgesics on the inflammatory pain state2014

    • Author(s)
      Yuta Aoki, Hirokazu Mizoguchi, Chizuko Watanabe, Tsukasa Sakurada, Shinobu Sakurada
    • Journal Title

      Neuroscience Letters

      Volume: 560 Pages: 122-125

    • DOI

      10.1016/j.neulet.2013.12.020

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potential Involvement of <i>μ</i>-Opioid Receptor Dysregulation on the Reduced Antinociception of Morphine in the Inflammatory Pain State in Mice2014

    • Author(s)
      Yuta Aoki, Hirokazu Mizoguchi, Chizuko Watanabe, Kumiko Takeda, Tsukasa Sakurada,Shinobu Sakurada
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 124 Issue: 2 Pages: 258-266

    • DOI

      10.1254/jphs.13242FP

    • NAID

      130003391472

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception2013

    • Author(s)
      Soh Katsuyama, Hirokazu Mizoguchi, Hikari Kuwahata, Takaaki Komatsu, Kohshi Nagaoka, Hitoshi Nakamura, Giacinto Bagetta, Tsukasa Sakurada, Shinobu Sakurada
    • Journal Title

      European Journal of Pain

      Volume: 17 Issue: 5 Pages: 664-675

    • DOI

      10.1002/j.1532-2149.2012.00242.x

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distinct physiological role of amidino-TAPA-sensitive and DAMGO-insensitive μ-opioid receptor splice variants in the mouse spinal cord2013

    • Author(s)
      Hirokazu Mizoguchi, Chizuko Watanabe, Takayuki Higashiya, Satoshi Takeda, Kaori Moriyama, Akihiko Yonezawa, Takashi Kon-no, Hirokazu Takagi, Tsukasa Sakurada, Shinobu Sakurada
    • Journal Title

      Eur. J. Pharmacol.

      Volume: 711 Issue: 1-3 Pages: 80-86

    • DOI

      10.1016/j.ejphar.2013.04.014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of spinal release ofα-neo-endorphin on the antinociceptive effect of TAPA2013

    • Author(s)
      Hirokazu Mizoguchi, Takashi Kon-no, Hiroyuki Watanabe, Chizuko Watanabe, Akihiko Yonezawa, Takumi Sato, Tsukasa Sakurada, Shinobu Sakurada
    • Journal Title

      Peptides

      Volume: 50 Pages: 139-144

    • DOI

      10.1016/j.peptides.2013.10.003

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Nalfurafineの末梢性抗掻痒作用2016

    • Author(s)
      音羽亮、溝口広一、渡辺千寿子、長瀬博、櫻田忍
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Hemokinin-1誘発性疼痛関連行動の発現機構2016

    • Author(s)
      渡辺千寿子、溝口広一、音羽亮、櫻田忍
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Amidino-TAPAの非依存性に関わるμオピオイド受容体スプライスバリアントの探索2016

    • Author(s)
      溝口広一、渡辺千寿子、音羽亮、吉岡麻也、櫻田忍
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] ラベンダーオイルの末梢局所投与によるパクリタキセル誘発性末梢神経障害性疼痛抑制効果の検討2015

    • Author(s)
      勝山壮、音羽亮、倉本敬二、櫻田忍
    • Organizer
      第22回日本未病システム学会学術総会
    • Place of Presentation
      北海道大学学術交流会館(札幌)
    • Year and Date
      2015-10-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 多発性硬化症疼痛に対するオピオイド性鎮痛薬の効果2015

    • Author(s)
      溝口広一、渡辺千寿子、音羽亮、長瀬博、櫻田忍
    • Organizer
      第9回日本緩和医療薬学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 当院における入院患者を対象としたアロマトリートメント(精油成分)による疼痛緩和作用の検討<第一報>2015

    • Author(s)
      真井健吾、椎崎正秀、前間邦生、楠直子、池末いづみ、桑波田日香里、勝山壮、小松生明、櫻田司、櫻田忍
    • Organizer
      第9回日本緩和医療薬学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Amidino-TAPAの非依存性に関わるμオピオイド受容体スプライスバリアントの探索2015

    • Author(s)
      溝口広一、渡辺千寿子、音羽亮、吉岡麻也、櫻田忍
    • Organizer
      第45回日本神経精神薬理学会・第37回日本生物学的精神医学会合同年会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 難治性掻痒症治療薬nalfurafineの末梢性抗掻痒作用2015

    • Author(s)
      音羽亮、小笠原蓉子、新井田隆宏、溝口広一、渡辺千寿子、勝山壮、長瀬博、櫻田忍
    • Organizer
      第66回日本薬理学会北部会
    • Place of Presentation
      富山国際会議場(富山)
    • Year and Date
      2015-09-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Effects of narcotic analgesics on the multiple sclerosis-related pain2015

    • Author(s)
      Hirokazu Mizoguchi, Takahiro Sumi, Chizuko Watanabe, Asuna Ohtsuki, Hiroshi Nagase, Shinobu Sakurada
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 神経障害性疼痛に対するmethadoneの脊髄鎮痛作用2014

    • Author(s)
      角貴祐、溝口広一、渡辺千寿子、櫻田忍
    • Organizer
      第126回日本薬理学会近畿部会
    • Place of Presentation
      和歌山県JAビル(和歌山)
    • Year and Date
      2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 多発性硬化症疼痛に対するオピオイド性鎮痛薬の効果2014

    • Author(s)
      溝口広一、渡辺千寿子、長瀬博、櫻田忍
    • Organizer
      第126回日本薬理学会近畿部会
    • Place of Presentation
      和歌山県JAビル(和歌山)
    • Year and Date
      2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 各種難治性疼痛に対する麻薬性鎮痛薬の効果2014

    • Author(s)
      角貴祐、溝口広一、渡辺千寿子、櫻田忍
    • Organizer
      第65回日本薬理学会北部会
    • Place of Presentation
      コラッセふくしま(福島)
    • Year and Date
      2014-09-26 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 炎症性疼痛下における麻薬性鎮痛薬の鎮痛作用減弱機構2014

    • Author(s)
      溝口広一、渡辺千寿子、櫻田忍
    • Organizer
      平成26年度東北薬科大学創薬研究センターシンポジウム
    • Place of Presentation
      東北薬科大学(仙台)
    • Year and Date
      2014-06-14
    • Related Report
      2014 Research-status Report
  • [Presentation] Hemokinin-1誘発性疼痛関連行動の発現機構2014

    • Author(s)
      渡辺千寿子、溝口広一、櫻田忍
    • Organizer
      平成26年度東北薬科大学創薬研究センターシンポジウム
    • Place of Presentation
      東北薬科大学(仙台)
    • Year and Date
      2014-06-14
    • Related Report
      2014 Research-status Report
  • [Presentation] Antinociceptive effect of narcotic analgesics against mechanical allodynia in inflammatory pain state2014

    • Author(s)
      Yuta Aoki, Hirokazu Mizoguchi, Chizuko Watanabe, Akihiko Yonezawa, Shinobu Sakurada
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] The antinociceptive effect of opioid analgesics in neuropathic cancer pain2014

    • Author(s)
      Ryou Sugawara, Hirokazu Mizoguchi, Chizuko Watanabe, Akihiko Yonezawa, Syu-ichi Kanno, Masaaki Ishikawa, Hiroshi Nagase, Shinobu Sakurada
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] Antinociceptive effect of narcotic analgesics in neuropathic pain state2014

    • Author(s)
      Takahiro Sumi, Hirokazu Mizoguchi, Chizuko Watanabe, Akihiko Yonezawa, Shinobu Sakurada
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] Antipruritic effect of kappa-opioid receptor agonist in mice2014

    • Author(s)
      Takahiro Niida, Hirokazu Mizoguchi, Chizuko Watanabe, Akihiko Yonezawa, Hiroshi Nagase, Shinobu Sakurada
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] Phosphorylation of mu opioid receptor reduced morphine analgesia in inflammatory pain state2013

    • Author(s)
      Yuta Aoki, Hirokazu Mizoguchi, Chizuko Watanabe, Akihiko Yonezawa, Tsukasa Sakurada, Shinobu Sakurada
    • Organizer
      International Narcotic Research Conference
    • Place of Presentation
      Pullman Cairns International (Cairns, Australia)
    • Related Report
      2013 Research-status Report
  • [Presentation] Effectiveness of amidino-TAPA against morphine-resistant neuropathic pain2013

    • Author(s)
      Hirokazu Mizoguchi, Chizuko Watanabe, Akihiko Yonezawa, Tsukasa Sakurada, Shinobu Sakurada
    • Organizer
      International Narcotic Research Conference
    • Place of Presentation
      Pullman Cairns International (Cairns, Australia)
    • Related Report
      2013 Research-status Report
  • [Presentation] 多発性硬化症疼痛に対する麻薬性鎮痛薬の効果2013

    • Author(s)
      溝口広一、渡辺千寿子、米澤章彦、長瀬博、櫻田司、櫻田忍
    • Organizer
      第33回鎮痛薬・オピオイドペプチドシンポジウム
    • Place of Presentation
      神戸大学(神戸)
    • Related Report
      2013 Research-status Report
  • [Presentation] 多発性硬化症疼痛に対する麻薬性鎮痛薬の効果

    • Author(s)
      溝口広一、渡辺千寿子、米澤章彦、櫻田忍
    • Organizer
      平成25年度東北薬科大学創薬研究センターシンポジウム
    • Place of Presentation
      東北薬科大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] μ受容体作動薬ADAMBの脊髄における抗侵害作用発現機序

    • Author(s)
      青木祐太、溝口広一、渡辺千寿子、米澤章彦、櫻田忍
    • Organizer
      平成25年度東北薬科大学創薬研究センターシンポジウム
    • Place of Presentation
      東北薬科大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] 脊髄疼痛伝達機構に対するμ受容体サブクラスの多様的制御の解析

    • Author(s)
      高木宏和、溝口広一、渡辺千寿子、米澤章彦、櫻田忍
    • Organizer
      第52回日本薬学会東北支部大会
    • Place of Presentation
      東北大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] デルモルフィン誘導体TAPAの脊髄鎮痛作用発現機構

    • Author(s)
      今野崇、溝口広一、渡辺千寿子、米澤章彦、櫻田忍
    • Organizer
      第52回日本薬学会東北支部大会
    • Place of Presentation
      東北大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] 神経絞扼性癌性疼痛における麻薬性鎮痛薬の効果

    • Author(s)
      菅原陵、溝口広一、渡辺千寿子、米澤章彦、菅野秀一、石川正明、櫻田忍
    • Organizer
      第52回日本薬学会東北支部大会
    • Place of Presentation
      東北大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] 神経障害性疼痛における末梢性TRPV1受容体及びNMDA受容体の関与

    • Author(s)
      遠藤有里子、溝口広一、渡辺千寿子、米澤章彦、櫻田忍
    • Organizer
      第52回日本薬学会東北支部大会
    • Place of Presentation
      東北大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] 神経障害性疼痛における各種麻薬性鎮痛薬の効果

    • Author(s)
      角貴祐、溝口広一、渡辺千寿子、米澤章彦、櫻田忍
    • Organizer
      第52回日本薬学会東北支部大会
    • Place of Presentation
      東北大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] CB1受容体拮抗薬AM251はERKの活性化を介して疼痛関連行動を起こす

    • Author(s)
      長岡高史、勝山壮、溝口広一、小松生明、渡辺千寿子、米澤章彦、櫻田司、櫻田忍
    • Organizer
      第52回日本薬学会東北支部大会
    • Place of Presentation
      東北大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Book] Aromatherapy: Basic Mechanisms and Evidence Based Clinical Use2015

    • Author(s)
      Laura Rombola, Luigi Antonio Morrone, Chizuko Watanabe, Hirokazu Mizoguchi, Tsukasa Sakurada, Laura Berliocchi, Maria Tiziana Corasaniti, Giacinto Bagetta, Shinobu Sakurada
    • Total Pages
      461
    • Publisher
      CRC Press
    • Related Report
      2015 Annual Research Report
  • [Book] Aromatherapy: Basic Mechanisms and Evidence Based Clinical Use2015

    • Author(s)
      Soh Katsuyama, Takaaki Komatsu, Giacinto Bagetta, Shinobu Sakurada, Tsukasa Sakurada
    • Total Pages
      461
    • Publisher
      CRC Press
    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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