Methadone-used new therapy for morphine-resistant intractable pain

• Project/Area Number: 15K08678
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Mizoguchi Hirokazu 東北医科薬科大学, 薬学部, 教授 (30360069)
• Co-Investigator(Kenkyū-buntansha): 桜田 忍 東北医科薬科大学, 薬学部, 客員教授 (30075816) ; 渡辺 千寿子 東北医科薬科大学, 薬学部, 准教授 (90296020)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 多発性硬化症疼痛 / 難治性疼痛 / Morphine / Methadone / NMDA受容体

Outline of Final Research Achievements

The analgesic effect of morphine is reduced in the condition of sciatic nerve ligation-induced neuropathic pain, inflammatory pain and multiple sclerosis-related pain. In the present study, we found that the single injection of methadone recovered the reduced morphine analgesia observed in those morphine-resistant intractable pain through a blockade of NMDA receptor.

Research Products

• [Journal Article] Neuropharmacological properties of the essential oil of bergamot for the clinical management of pain-related BPSDs (2018)
  • Author(s): Damiana Scuteri, Laura Rombola, Laura Tridico, Hirokazu Mizoguchi, Chizuko Watanabe, Tsukasa Sakurada, Shinobu Sakurada, Maria Tiziana Corasanit, Giacinto Bagetta, Luigi Antonio Morrone
  • Journal Title: Current Medicinal Chemistry Volume: 印刷中 Issue: 20 Pages: 3764-3774
  • DOI: 10.2174/0929867325666180307115546
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The involvement of spinal release of histamine on nociceptive behaviors induced by intrathecally administered spermine. (2017)
  • Author(s): Mizoguchi H, Watanabe C, Hayashi T, Iwata Y, Watanabe H, Katsuyama S, Hamamura K, Sakurada T, Ohtsu H, Yanai K, Sakurada S.
  • Journal Title: European Journal of Pharmacology Volume: 800 Pages: 9-15
  • DOI: 10.1016/j.ejphar.2017.01.031
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Bergamot essential oil attenuates anxiety-like behaviour in rats (2017)
  • Author(s): Laura Rombola, Laura Tridico, Damiana Scuteri, Tsukasa Sakurada, Shinobu Sakurada, Hirokazu Mizoguchi, Pinarosa Avato, Maria Tiziana Corasaniti, Giacinto Bagetta, Luigi Antonio Morrone
  • Journal Title: Molecules Volume: 22 Issue: 4 Pages: 614-614
  • DOI: 10.3390/molecules22040614
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Opioids resistance in chronic pain management (2017)
  • Author(s): Luigi A. Morrone, Damiana Scuteri, Laura Rombola, Hirokazu Mizoguchi, Giacinto Bagetta
  • Journal Title: Current Neuropharmacology Volume: 15 Issue: 3 Pages: 444-456
  • DOI: 10.2174/1570159x14666161101092822
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Analgesic Effects of 1st Generation Anti-histamines in Mice (2016)
  • Author(s): Mebae Takahashi, Kazuhiro Shima, Masahiro Tsuchiya, Yoshihiro Hagiwara, Hirokazu Mizoguchi, Shinobu Sakurada, Shunji Sugawara, Takuo Fujita, Takeshi Tadano, Makoto Watanabe, Satoshi Fukumoto, Yasuo Endo
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 4 Pages: 620-624
  • DOI: 10.1248/bpb.b15-00755
  • NAID: 130005141684
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intrathecal morphine-3-glucuronide-induced nociceptive behavior via δ-2 opioid receptors in the spinal cord (2016)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Involvement of spinal glutamate in nociceptive behavior induced by intrathecal administration of hemokinin-1 in mice (2016)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 依存性のない新規鎮痛薬の探索 (2018)
  • Author(s): 溝口広一
  • Organizer: 第2回仙台痛みフォーラム
  • Invited
• [Presentation] 天然由来成分の抗かゆみ活性 (2018)
  • Author(s): 芦部文一朗、松見繁、丸山徹也、溝口広一、櫻田忍
  • Organizer: 日本薬学会第138年会
• [Presentation] 炎症性疼痛下における各種麻薬性鎮痛薬における鎮痛効果とその耐性形成能 (2017)
  • Author(s): 込山麻美、溝口広一、渡辺千寿子、音羽亮、櫻田忍
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール（長崎県・長崎市）
  • Year and Date: 2017-03-15
• [Presentation] 多発性硬化症疼痛に対する麻薬性鎮痛薬の効果 (2017)
  • Author(s): 溝口広一、渡辺千寿子、音羽亮、櫻田忍
  • Organizer: 平成29年度東北医科薬科大学創薬研究センターシンポジウム
• [Presentation] 炎症性疼痛下における麻薬性鎮痛薬の鎮痛効果ならびに鎮痛耐性形成 (2017)
  • Author(s): 込山麻美、渡辺千寿子、音羽亮、櫻田忍、溝口広一
  • Organizer: 平成29年度東北医科薬科大学創薬研究センターシンポジウム
• [Presentation] Amidino-TAPAの神経障害性疼痛に対する有効性 (2017)
  • Author(s): 溝口広一、渡辺千寿子、音羽亮、櫻田忍
  • Organizer: 第4回包括的緩和医療科学学術研究会・第5回Tokyo疼痛緩和次世代研究会合同研究会
• [Presentation] Effectiveness of amidino-TAPA against morphine-resistant neuropathic pain (2017)
  • Author(s): Hirokazu Mizoguchi、Chizuko Watanabe、Akira Otowa、Shinobu Sakurada
  • Organizer: 第60回日本神経化学会大会
• [Presentation] 難治性掻痒症治療薬nalfurafineの末梢性抗掻痒作用 (2017)
  • Author(s): 音羽亮、渡辺千寿子、長瀬博、櫻田忍、溝口広一
  • Organizer: 第68回日本薬理学会北部会
• [Presentation] 炎症性疼痛制御におけるmethadoneの特異的作用 (2017)
  • Author(s): 込山麻美、渡辺千寿子、音羽亮、櫻田忍、溝口広一
  • Organizer: 第68回日本薬理学会北部会
• [Presentation] 炎症性疼痛下における各種麻薬性鎮痛薬の鎮痛効果とその耐性形成能 (2016)
  • Author(s): 込山麻美、溝口広一、渡辺千寿子、音羽亮、櫻田忍
  • Organizer: 第67回日本薬理学会北部会
  • Place of Presentation: 北海道大学（北海道・札幌市）
  • Year and Date: 2016-09-30
• [Presentation] 神経障害性疼痛に対する麻薬性鎮痛薬ならびに新規鎮痛薬の効果 (2016)
  • Author(s): 溝口広一、渡辺千寿子、音羽亮、櫻田忍
  • Organizer: 平成28年度東北医科薬科大学創薬研究センターシンポジウム
  • Place of Presentation: 東北医科薬科大学（宮城県・仙台市）
  • Year and Date: 2016-06-18
• [Presentation] 炎症性疼痛下における各種麻薬性鎮痛薬の鎮痛効果とその耐性形成能 (2016)
  • Author(s): 込山麻美、溝口広一、渡辺千寿子、音羽亮、櫻田忍
  • Organizer: 平成28年度東北医科薬科大学創薬研究センターシンポジウム
  • Place of Presentation: 東北医科薬科大学（宮城県・仙台市）
  • Year and Date: 2016-06-18
• [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
• [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
• [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
• [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
• [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
• [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
• [Book] トワイクロス先生の緩和ケア処方薬 第2版 (2017)
  • Author(s): 武田 文和、鈴木勉 監訳
  • Total Pages: 887
  • Publisher: 医学書院
  • ISBN: 9784260030311
• [Book] 疾患薬理学 (2016)
  • Author(s): 溝口広一
  • Total Pages: 862
  • Publisher: Neo Medical
• [Book] Aromatherapy: Basic Mechanisms and Evidence Based Clinical Use (2015)
  • Author(s): Laura Rombola, Luigi Antonio Morrone, Chizuko Watanabe, Hirokazu Mizoguchi, Tsukasa Sakurada, Laura Berliocchi, Maria Tiziana Corasaniti, Giacinto Bagetta, and Shinobu Sakurada
  • Total Pages: 461
  • Publisher: CRC Press