Elucidation of the role of bioactive lipids and local inflammatory responses related to the onset and the chronicity of CRPS

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11103
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: The University of Tokyo
• Principal Investigator: Ito Nobuko 東京大学, 医学部附属病院, 講師 (80332609)
• Co-Investigator(Kenkyū-buntansha): 山田 芳嗣 東京大学, 医学部附属病院, 教授 (30166748)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脂質 / 疼痛学 / 神経科学

Outline of Final Research Achievements

Bioactive lipids of wound site were analyzed in a postoperative pain model at risk for CRPS. The arachidonic acid-derived lipids and the EPA-derived lipids having an anti-inflammatory effect were increased. It was suggested that the balance of production of inflammatory and anti-inflammatory lipids affects postoperative pain. The effects of lysophosphatidic acid LPA on acute pain and lumbar spinal canal stenosis (CEC) were investigated together with the production pathway. Acute pain reaction was suppressed by LPA receptor antagonist administration, and it was found that LPA signal was involved in acute pain. In the CEC model, specific LPA species increased with their corresponding precursor LPC species in cerebrospinal fluid. LPC was detected in the local area where compression damage was induced, suggesting that LPA was produced by the converting enzyme ATX from LPC.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

定量が難しく病態での役割解明が困難であった生理活性脂質について、微量組織から多種脂質分子を同時定量できる測定系を用いて信頼性の高い脂質定量情報が得られた。副作用の多い非ステロイド性鎮痛薬以外の鎮痛薬ターゲットの探索が期待される。
通常では髄液検出がほとんどされないLPAと前駆体LPCが、腰部脊柱管狭窄症モデル髄液で早期より検出された。難治性神経障害性疼痛の治療ターゲットとして髄液におけるLPA産生経路が提示された。これらの結果は神経障害性疼痛患者髄液中のデータと同様であり、このモデルが難治性疼痛発生におけるLPAシグナル伝達の役割を評価するのに適切であることが分かった