Inflammatory-independent pain mechanism via to VEGF/neuropeptide axis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kitasato University
• Principal Investigator: Takaso Masashi 北里大学, 医学部, 教授 (90439117)
• Co-Investigator(Kenkyū-buntansha): 内田 健太郎 北里大学, 医学部, 講師 (50547578) ; 大久保 直 北里大学, 医学部, 准教授 (10450719) ; 岩瀬 大 北里大学, 医学部, 助教 (30406946) ; 井上 玄 北里大学, 医学部, 准教授 (80594209)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 血管内皮増殖因子 / 疼痛 / 神経ペプチド / Apelin

Outline of Final Research Achievements

Research suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear. We investigated the role of VEGF in the osteoarthritic pain pathway. Expression levels of VEGF were positively correlated with pain score, VAS. VEGF-positive cells were identified in the lining of the synovium. Expression of apelin mRNA and protein were significantly elevated in synovial cells treated with exogenous VEGF. Synovial apelin expression levels correlate with VAS. TGF-beta regulated VEGF expression through the canonical and non-canonical pathway. TGF/VEGF/Apelin axis play an important role for inflammation-independent pain in patients with osteoarthritis.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

疼痛の慢性化による我が国の経済損失は3,700億円と推定されており、疼痛治療法メカニズムの解明および疼痛治療法の開発は、社会的、経済的基盤の改善に極めて重要な意義を持っている。本研究成果は、血管内皮増殖因子（VEGF）の上流ならびに下流を標的とした変形性関節症患者の疼痛治療の新たな治療標的を供給するもである。