Study for the mechanism underlying neuropathic pain by manipulating the membrane phospholipid

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16938
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Shota Yamamoto 国立研究開発法人国立国際医療研究センター, その他部局等, 特任研究員 (50825693)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 神経障害性疼痛 / 生体膜リン脂質 / リゾリン脂質アシル転移酵素 / 脂質メディエーター

Outline of Final Research Achievements

Neuropathic pain is a pathological chronic pain condition that occurs after nerve injury, and the underlying mechanisms remain unclear. Glycerophospholipids (PLs) play essential roles in our body, such as main structural components of biological membranes and precursors of bioactive lipid mediators. Over the last ten years, lysophospholipid acyltransferases (LPLATs) have been identified as the responsible genes to generate PLs diversity. In this study, we revealed that peripheral nerve injury (PNI) induced dynamic changes of PLs composition and increase of lipid mediators in the dorsal root ganglia and spinal cord. Using several mice lines lacking LPLAT gene, we found that PNI-induced chronic pain was attenuated in these mice. These findings suggest that LPLATs may be the novel target molecules to treat chronic pain.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

生体膜リン脂質の多様性の生理・病態学的な意義についてはほとんどブラックボックスである。本研究では，神経障害性疼痛病態時における膜リン脂質組成の変化や，リン脂質を前駆体とする脂質メディエーターの産生増加が疼痛症状の発症維持に寄与することを明らかにした。膜リン脂質組成の変化が疼痛に繋がる詳細なメカニズムについてはさらなる検討が必要だが，リン脂質多様性を制御するLPLAT欠損マウスにて疼痛軽減の表現型が得られたことは，今後のリン脂質多様性の生物学において学術的意義が認められる。