Role of BEGAIN for central sensitization in the spinal dorsal horn

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09001
• 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, 准教授 (60469244)
• Co-Investigator(Kenkyū-buntansha): 伊藤 誠二 大阪医科大学, その他部局等, 客員教授 (80201325) ; 西田 和彦 関西医科大学, 医学部, 助教 (80448026)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 慢性疼痛 / 脊髄後角 / BEGAIN / NMDA受容体 / 神経障害性疼痛

Outline of Final Research Achievements

To clarify the molecular function of brain enriched guanylate kinase associated protein (BEGAIN) in the spinal dorsal horn, we performed electrophysiological recording of NMDA receptor, immunohistochemistry for BEGAIN and synaptic marker proteins, PSD-95 and synaptophysin, and in situ hybridization for BEGAIN in the spinal cord. In these analyses, we identified the relationship between BEGAIN and NMDA receptor as a delay of time to peak of EPSC in SG neurons of BEGAIN knockout mouse and the synaptic localization of BEGAIN in the spinal laminae Iii-IIIo. These results and previous results by us indicate that BEGAIN is involved in the mechanical allodynia in neuropathic pain concerned with the action of NMDA receptor. Furthermore, broad distribution of BEGAIN-positive neurons in not only spinal dorsal horn but also spinal ventral horn was demonstrated by in situ hybridization.

Free Research Field

神経科学　疼痛学

Academic Significance and Societal Importance of the Research Achievements

これまで、機能が不明であったBEGAINという蛋白質を、慢性疼痛の発症維持に関与する分子として、詳細な分子機序について解析をおこなった。そしてBEGAINは、脊髄のニューロンにおいてシナプスに局在し、NMDA受容体との機能的相互作用を介し、疼痛病態での異常感覚の発生に関与することを明らかにした。慢性疼痛に関わるタンパク質の同定と機能解析は、将来の創薬につながる能性があることから、BEGAINの研究成果と今後のより詳細なBEGAINの分子基盤における成果は、疼痛発症機序の解明という学術的意義だけでなく、慢性疼痛患者を対照とした創薬研究の創出という社会的意義も大きいものである。