Role of exosomes in the aggravation of neuropathic pain

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16936
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Daiichi University, College of Pharmaceutical Sciences
• Principal Investigator: Hamamura Kengo 第一薬科大学, 薬学部, 助教 (30756466)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: エクソソーム / 神経障害性疼痛 / ホルマリン誘発侵害刺激行動

Outline of Final Research Achievements

Exosomes are small (50-150 nm) membrane vesicles of endocytic origin that are found in bodying fluids, and supporting their role in intercellular communication. Although recent studies have demonstrated that various biomarkers involved in the extent of pain from the serum exosomes, the effects of exosomes on pain have not been elucidated.
We have confirmed that 0.5% formalin-induced nociceptive response was significantly enhanced by intrathecal (i.t.) pre-treatment with serum exosomes isolated from partial sciatic nerve ligation (PSNL) but not from sham-operated mice. In addition, exosomes isolated from PSNL were digested with trypsin or exosomes structure was disrupted by surfactant treatment were ineffective on formalin-induced response.
In this study, complement C5, which was found by proteomic and other analysis, located on the exosomal membrane derived from PSNL mouse serum plays an important role in potentiating formalin-induced nociceptive behavior.

Free Research Field

疼痛学

Academic Significance and Societal Importance of the Research Achievements

エクソソーム研究は、がんの診断マーカーの探索やドラッグデリバリーシステム (DDS) の領域で盛んに行われている。本研究では、初めてエクソソームと神経障害性疼痛の病態悪化とを関連付けた。また、従来までのエクソソーム研究がバイオマーカーの探索等で着目されたエクソソームの内腔に主眼を置いた研究であるのに対し、本研究におけるアプローチは膜外領域である二重膜上の膜タンパク質に着目している点で大きく異なる。エクソソームと病態進行との関連性に焦点を当てることで、病態の解明や創薬、さらには老化や疾患の予防といった健康増進を指向した応用研究への移行にも貢献できるものと考える。