Reproduction of chronic pain model through a reconstitution of neuronal circuit components including LPA priming and iPS cells, and its application for drug discovery

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253077
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Nagasaki University
• Principal Investigator: UEDA Hiroshi 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (00145674)
• Co-Investigator(Kenkyū-buntansha): 松永 隼人 長崎大学, 医歯薬学総合研究科(薬学系), 客員研究員 (20437833) ; 永井 潤 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (20608369) ; 水田 賢志 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (50717618) ; 田中 義正 長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (90280700) ; 水谷 龍明 京都大学, ウイルス研究所, 助教 (50701843) ; 内田 仁司 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (30549621)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 脂質メディエーター / LPA受容体 / 神経障害性疼痛 / 線維筋痛症 / フィードフォワード機構 / in vio再構成 / ミクログリア / アストロサイト

Outline of Final Research Achievements

We clarified that LPA signals play roles in the development and maintenance of various types of neuropathic pain models and various types of fibromyalgia models. We then performed the high throughput and in silico screening of inhibitors and their chemical optimizations, and successfully obtained biochemical tools to clarify molecular mechanisms underlying chronic pain and therapeutic lead compounds for drug development. As chronic pain was found to comprise of multiple feed-forward systems including immune system, we performed the in vivo reconstitution of LPA-primed cells (microglia, astrocytes, iPS cells, T-cells). From these studies, we found LPA3-microglia-cytokine and LPA1-astrocytes-chemokine production are involved in the development and maintenance of chronic pain, respectively.

Free Research Field

薬理学