Analysis of brain-enriched guanylate kinase-associated protein (BEGAIN) as a novel neuropathic pain-related protein in spinal lamina Iii

• Project/Area Number: 25460729
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Kansai Medical University
• Principal Investigator: KATANO Tayo 関西医科大学, 医学部, 講師 (60469244)
• Co-Investigator(Kenkyū-buntansha): ITO Seiji 関西医科大学, 医学部, 教授 (80201325)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 神経障害性疼痛 / BEGAIN / プロテオミクス / 脊髄後角 / IIi層 / PSD / シナプス / 慢性疼痛 / 神経可塑性

Outline of Final Research Achievements

Maintenance of neuropathic pain caused by peripheral nerve injury critically depends on the phosphorylation of GluN2B, a subunit of NMDA receptor, at Tyr1472 (Y1472). Here we took an advantage of comparative proteomic analysis between wild-type and knockin mice with a mutation of Y1472 to Phe of GluN2B (Y1472F-KI) to search for PSD proteins in the spinal dorsal horn that mediate signaling of neuropathic pain downstream of phosphorylated Y1472 GluN2B.　We identified brain-enriched guanylate kinase-associated protein (BEGAIN) as increased protein in wild-type, but not in Y1472F-KI mouse after peripheral nerve injury by proteomic analysis.
BEGAIN was localized in spinal lamina IIi. Moreover, neuropathic pain, but not physiological pain was significantly attenuated in the knockout mice of BEGAIN. These results indicate that BEGAIN was involved in pathological pain transmission through NMDAR activation following the phosphorylation of GluN2B at Y1472 in spinal lamina IIi.

Research Products

• [Journal Article] Role of c-Jun N-terminal kinase in late nerve regeneration monitored by in vivo imaging of thy1-yellow fluorescent protein transgenic mice. (2016)
  • Author(s): Nguyen H. T., Katano, T., Matsumura, S., Pham M. V., Muratani, T., Minami, T. and Seiji Ito.
  • Journal Title: Eur. J. Neurosci. Volume: 43 Issue: 4 Pages: 548-560
  • DOI: 10.1111/ejn.13139
  • Peer Reviewed / Open Access
• [Journal Article] 脊髄に起因する痛み~脊髄の構造と慢性化をおこす中枢性感作~ Chronic pain is induced by central sensitization in spinal dorsal horn. (2015)
  • Author(s): 片野泰代、伊藤誠二
  • Journal Title: Practice of Pain Management Volume: 第18号, (Vol.6, No.1) Pages: 22-25
• [Journal Article] Identification of nitrated tyrosine residues of protein kinase G-Ia by mass spectrometry. (2014)
  • Author(s): Lu J, Yao I, Shimojo M, Katano T, Uchida H, Setou M, Ito S
  • Journal Title: Analytical and bioanalytical chemistry Volume: 406 Issue: 5 Pages: 1387-1396
  • DOI: 10.1007/s00216-013-7535-4
  • Peer Reviewed
• [Journal Article] Involvement of Nax sodium channel in peripheral nerve regeneration via lactate signaling. (2013)
  • Author(s): Unezaki, S., Katano, T., Hiyama, T.Y., Nguyen, H. T., Yoshii, S., Noda, M., and Ito, S.
  • Journal Title: European Journal of Neuroscience Volume: 39 Issue: 5 Pages: 720-729
  • DOI: 10.1111/ejn.12436
  • Peer Reviewed / Open Access
• [Presentation] 脊髄後角における新規慢性疼痛関連分子の同定 (2015)
  • Author(s): 片野泰代、福田正史、山崎真耶、阿部学、渡辺雅彦、古江秀昌、矢尾育子、西田和彦、奥村宣明、中澤敬信、山本雅、崎村健司、高尾敏文、伊藤誠二
  • Organizer: 2015年度包括型脳科学研究推進支援ネットワーク 冬のシンポジウム
  • Place of Presentation: 一橋大学一橋講堂（東京・千代田区）
  • Year and Date: 2015-12-17
• [Presentation] New mechanisms for pain control and clinical potential. (2015)
  • Author(s): Nguyen H. Tu, Tayo Katano, Shinji Matsumura and Seiji Ito
  • Organizer: International Conference on Pain-Anesthesiology and pain control
  • Place of Presentation: Hanoi (Vietnam)
  • Year and Date: 2015-11-20
  • Int'l Joint Research
• [Presentation] Involvement of c-Jun N-terminal kinase in neurite extension of cultured DRG neurons. (2015)
  • Author(s): Nguyen, H. T., Matsumura, S. Katano, T., and Ito, S.
  • Organizer: The 45th annual meeting of the Society for Neuroscience
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Localization of neuropathic pain-related protein, BEGAIN in the spinal dorsal horn. (2015)
  • Author(s): Katano, T., Watanabe, M., Yamazaki, M., Abe, M., Yao, I., Sakimura, K. and Ito, S.
  • Organizer: The 45th annual meeting of the Society for Neuroscience
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Two feasible mouse models for neuropathy. (2015)
  • Author(s): Pham, M.V., Nguyen, H.T., Katano, T., Matsumura, S. and Ito, S.
  • Organizer: The 2nd Gene & Immunotherapy Conference in Vietnam
  • Place of Presentation: Ho Chi Minh (Vietnam)
  • Year and Date: 2015-09-25
  • Int'l Joint Research
• [Presentation] Involvement of c-Jun N-terminal kinase in peripheral nerve regeneration. (2014)
  • Author(s): Nguyen, H. T., Katano, T., Matsumura, S. and Ito, S.
  • Organizer: The 44th annual meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C.
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Involvement of endothelin in peripheral nerve regeneration. (2014)
  • Author(s): Ito, S., Nguyen, H. T., Matsumura, S. and Katano, T.
  • Organizer: The 44th annual meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C.
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] CaMKIIキナーゼ不活型KIマウスにおける慢性疼痛モデル脊髄後角のCaMKIIのシナプス局在 (2014)
  • Author(s): 矢尾育子、松村伸治、片野泰代、山肩葉子、井本敬二、伊藤誠二
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜（パシフィコ横浜）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 成熟した疼痛研究の新しい展開 New departure of mature pain research. (2014)
  • Author(s): 伊藤誠二、片野泰代、松村伸治、西田和彦
  • Organizer: 日本ペインクリニック学会第48回大会
  • Place of Presentation: 新宿（京王プラザホテル）
  • Year and Date: 2014-07-25
  • Invited
• [Presentation] 末梢神経再生モデルを用いた神経再生におけるエンドセリンの関与 Involvement of endothelin in peripheral nerve regeneration using tubing and osmotic pump model. (2014)
  • Author(s): Nguyen Huu Tu、片野泰代、松村伸治、伊藤誠二
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: 大阪（KKRホテルオーサカ）
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] Involvement of neuropathic pain-related protein-B(NPRP-B), a novel functional molecule, in inflammatory and neuropathic pain in vivo. (2013)
  • Author(s): Katano, T., Yao, I., Yamazaki, M., Abe, M., Fukuda, M., Okumura, N., Takao, T., Sakimura, K. and Ito, S.
  • Organizer: The 43rd annual meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, America
• [Presentation] Proteomic approach of nitrated tyrosine residues of protein kinase G-Iα. (2013)
  • Author(s): Ito, S., Lu, J., Shimojo, M., Katano, T., Uchida, H. and Yao, I.
  • Organizer: The 43rd annual meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, America
• [Presentation] Energy coupling of axon-Schwann cells by Nax and endothelin in nerve regeneration (2013)
  • Author(s): Nguyen H. T., Katano, T., Hiyama, Y. T., Noda, M. and Ito, S.
  • Organizer: The 44th NIPS International Symposium and The 5th Asian Pain Symposium
  • Place of Presentation: 岡崎コンファレンスセンター（岡崎市）
• [Book] Studies on Pediatric Disorders (Oxidative Stress in Applied Basic Research and Clinical Practice) (2014)
  • Author(s): Katano, T. Ito, S
  • Total Pages: 494
  • Publisher: Human Press