Prevention and treatment of chemotherapy-induced neuropathic pain and visceral pain by targeting HMBG1, a nuclear protein

• Project/Area Number: 26460710
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Kindai University
• Principal Investigator: KAWABATA Atsufumi 近畿大学, 薬学部, 教授 (20177728)
• Co-Investigator(Kenkyū-buntansha): 関口 富美子 近畿大学, 薬学部, 准教授 (90271410) ; 坪田 真帆 近畿大学, 薬学部, 助教 (90510123)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: HMGB1 / RAGE / CXCR4 / Toll-like receptor 4 / トロンボモジュリン / 神経障害性疼痛 / 内臓痛 / 膵臓痛 / ＨＭＧＢ１ / 膀胱痛 / TLR4 / 神経症障害性疼痛 / 結腸痛

Outline of Final Research Achievements

HMGB1, a nuclear protein, is released into the extracellular space and plays a role as one of damage-associated molecular patterns in pathological conditions. Here we analyzed the role of HMGB1 in chemotherapy-induced neuropathic pain and visceral pain. Our data indicate that HMGB1 participates in the development and maintenance of chemotherapy-induced neuropathic pain and pancreatitis-related pain.

Research Products

• [Journal Article] Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats (2016)
  • Author(s): Nishida, T., Tsubota, M., Kawaishi, Y., Yamanishi, H., Kawakami, N., Sekiguchi, F., Ishikura, H., Liu, K., Nishibori, M., Kawabata, A.
  • Journal Title: Toxocology Volume: 365 Pages: 48-58
  • DOI: 10.1016/j.tox.2016.07.016
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 膵炎の痛痛における侵害受容体の関与と治療への展望 (2016)
  • Author(s): 坪田真帆、川端篤史
  • Journal Title: 胆と膵 Volume: 37 Pages: 1535-1539
• [Journal Article] Peripheral HMGB1-induced hyperalgesia in mice: redox state-dependent distinct roles of RAGE and TLR4 (2016)
  • Author(s): Yamasoba, D., Tsubota, M., Domoto, R., Sekiguchi, F., Nishikawa, H., Liu, K., Nishibori, M., Ishikura, H., Yamamoto, T., Taga, A., Kawabata, A.
  • Journal Title: J. Pharmacol. Sci. Volume: 130 Issue: 2 Pages: 139-142
  • DOI: 10.1016/j.jphs.2016.01.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Roles of TLR4 and RAGE targeted by high mobility group box 1 in inflammatory and chemotherapy-induced peripheral neuropathy (2016)
  • Author(s): Kawabata, A.
  • Organizer: Topical Workshop “Toll-Like Receptor Pain Mechanisms” in 16th World Congress on Pain
  • Place of Presentation: パヒフィコ横浜（横浜）
  • Year and Date: 2016-09-26
  • Int'l Joint Research / Invited
• [Presentation] HMGB1研究の新展開 ～免疫系と神経系のクロストークにおける役割～ (2016)
  • Author(s): 川畑
  • Organizer: 第31回日本救命医療学会総会・学術集会 イブニングセミナー
  • Place of Presentation: アゴーラ福岡山の上ホテル＆スパ（福岡）
  • Year and Date: 2016-09-16
  • Invited
• [Presentation] トロンボモジュリンアルファの内臓痛治療への応用 (2016)
  • Author(s): 川畑篤史
  • Organizer: 第44回日本潰瘍学会 シンポジウム「医薬品の消化器病への適用拡大における理論構築 ～ これぞ消化器薬理の力」
  • Place of Presentation: 旭川グランドホテル（旭川）
  • Year and Date: 2016-09-02
  • Invited
• [Presentation] High mobility group box 1 mediates pancreatic pain in mice (2016)
  • Author(s): Kawabata, A., Irie, Y., Tsubota, M., Sekiguchi, F., Ishikura, H., Nishibori, M.
  • Organizer: Physiology 2016
  • Place of Presentation: Convention Centre Dublin（ダブリン）
  • Year and Date: 2016-07-28
  • Int'l Joint Research
• [Presentation] Macrophage-derived high mobility group box 1 participates in the development and maintenance of pancreatic pain through the activation of RAGE and CXCR4 in mice with cerulein-induced acute pancreatitis. (2015)
  • Author(s): Irie, Y., Tsubota, M., Sekiguchi, F., Ishikura, H., Nishibori, M., Kawabata, A.
  • Organizer: Neuroscience 2015
  • Place of Presentation: シカゴ、アメリカ
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Bladder pain accompanying cyclophosphamide-induced mouse cystitis involves HMGB1 release upstream of the cystathionine-gamma-lyase/H2S/Cav3.2 pathway in the bladder tissue (2015)
  • Author(s): Kawabata, A., Tsubota, M., Yamaguchi, K., Hiramoto, S., Sekiguchi, F., Tanaka, J., Ishikura, H., Nishibori, M.
  • Organizer: Neuroscience 2015
  • Place of Presentation: シカゴ、アメリカ
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] 内臓痛の新しい治療標的分子：T型Ca2+チャネルとHMGB1 (2015)
  • Author(s): 川畑篤史
  • Organizer: 生体機能と創薬シンポジウム2015
  • Place of Presentation: 日本大学（船橋）
  • Year and Date: 2015-08-27
  • Invited
• [Presentation] HMGB1を標的とする内臓痛治療(シンポジウム「HMGB1を標的とする治療の新規展開」） (2015)
  • Author(s): 坪田真帆、川畑篤史
  • 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
  • Invited
• [Presentation] High mobility group box 1 as a target for prevention and therapeutic treatment of chemotherapy-induced neuropathic pain. (2014)
  • Author(s): Kawabata, A., Kawaishi, Y., Nishida, T., Yamanishi, H., Kamitani, N., Tsubota, M., Sekiguchi, F., Ishikura, H., Nishibori, M.
  • Organizer: Pharmacology 2014
  • Place of Presentation: Queen Elizabeth II Conference Centre (イギリス・ロンドン)
  • Year and Date: 2014-12-16 – 2014-12-18
• [Presentation] Prevention and reversal of chemotherapy-induced neuropathic pain by HMGB1 neutralization in rodents (2014)
  • Author(s): Kawabata, A., Kawaishi, Y., Nishida, T., Yamanishi, H., Kamitani, N., Tsubota, M., Ishikura, H., Sekiguchi, F., Nishibori, M
  • Organizer: 9th FENS Forum of European Neuroscience
  • Place of Presentation: Mico - Milano Congressi (イタリア・ミラノ)
  • Year and Date: 2014-07-05 – 2014-07-09
• [Remarks]
  • URL: http://www.phar.kindai.ac.jp/byoutai/index.files/byoutai.htm
• [Remarks] 近畿大学薬学部病態薬理学研究室
  • URL: http://www.phar.kindai.ac.jp/byoutai/index.files/byoutai.htm