Elucidation and regulation of the action of disease-specific macrophages on chronic pain in osteoarthritis of the knee

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18523
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hoshino Takashi 東京医科歯科大学, 東京医科歯科大学病院, 助教 (70836923)
• Project Period (FY): 2020-03-01 – 2023-03-31
• Keywords: 膝関節

Outline of Final Research Achievements

Injection of 1.0 mg of monoiodoacetic acid into the knee of rats examined the cell dynamics. It was found that cell invasion and proliferation began on the 1st day after administration, and increased especially by the 5th day. Furthermore, cell proliferation occurred mainly in the superficial synovial membrane. The cells in the superficial synovial layer spread to the deep layer by being extruded by newly proliferating cells in the superficial layer. On the 5th to 7th days, the synovial cells with cell infiltration showed fibrosis, angiogenesis, and neurogenesis accompanying the blood vessels. Pain avoidance behavior by the incapacity test continued during and after this period, leading from acute inflammation to chronic pain. We consider that the simultaneous changes in cells and tissues are a phenomenon that can be said to be one of the mechanisms by which acute inflammation becomes chronic pain.

Free Research Field

整形外科学分野

Academic Significance and Societal Importance of the Research Achievements

軟骨変性を主体とする膝変形性関節症の罹患者数は日本国内の4の内820万人以上が膝の慢性疼痛に悩んでいる。一方で、このように高い罹患率にもかかわらず，慢性疼痛発症の病態の科学的検証は不足している。そのため進行機序に基づいた疾患修飾型治療法は無い。炎症誘発物質（モノヨード酢酸）のラット膝関節内への注射は関節炎を誘発し、続いて骨軟骨破壊を起こすため、膝の慢性疼痛モデルとして知られている。インキャパスタンステストによる疼痛回避行動はこの間そして、その後へと継続しており、急性の炎症から慢性疼痛へと続いていた。同時期の細胞と組織の変化は急性の炎症が慢性疼痛へとなる機序の一旦と言える現象であると考察する。