Biological significance of the mechanically activated channel associated with mechanical pain in knee osteoarthritis

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Ikeda Ryo 東京慈恵会医科大学, 医学部, 講師 (20439772)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 変形性膝関節症 / 機械性痛覚過敏 / 異痛症 / Piezo

Outline of Final Research Achievements

Knee osteoarthritis (OA) increase mechanical pain sensitivity under sustained weight bearing and joint movements due to its irreversible degenerative changes to the knee joint. This unpleasant arthralgia induces functional disturbance and reduces QOL of those affected. Understanding the mechanisms of the mechanical hyperalgesia and allodynia might provide a target for relief pain in patients with such symptoms. Piezo channel is mechanically activated ion channel and transduces information regarding injury to the articular cartilage. However, whether expression levels are influenced by knee OA has remained unknown. We measured Piezo mRNA in knee joints and dorsal root ganglia after establishing a model of knee osteoarthritis in rodents using monosodium iodoacetate and found that Piezo mRNA synthesis is not upregulated. Further studies will need to be performed to proof biological significance of Piezo channel for mechanical pain in knee OA.

Free Research Field

整形外科　疼痛

Academic Significance and Societal Importance of the Research Achievements

2010年に同定された機械作動性チャネルPiezoは、病態解明が急務とされている神経障害性疼痛などの難治性慢性痛成立に深く関わることが報告されている。近年、膝関節軟骨損傷の情報伝達を担い、炎症性物質によって機能修飾されることも明らかになったため、罹患率の高い膝OAの機械性疼痛成立においても、その関与が推察されていた。本研究結果ではチャネル発現量に変化を認めなかったが、既存のPiezoチャネルの機能亢進が機械性疼痛成立にどのように関連するか問題提起できたと考える。膝OAの機械性疼痛におけるPiezoチャネルの生物学的意義を深く証明するためには、さらなる研究継続が必須と考える。