Identification of pain-specific nerve growth factor (NGF)-mediated signalings using painless NGF and application to painless nerve regeneration therapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17821
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Keio University
• Principal Investigator: KATO Jungo 慶應義塾大学, 医学部(信濃町), 講師 (40465018)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 痛み / 慢性痛 / 神経成長因子 / 神経再生 / p75

Outline of Final Research Achievements

We have attempted to develop a novel analgesic by targeting pain-specific nerve growth factor-mediated signal pathways. We produced F(ab’)2 fragments from anti-NGF monoclonal antibody NGF30 that reportedly specifically inhibits NGF-p75 interactions. The NGF30- F(ab’)2 fragments facilitated the NGF-induced internalization of NGF cognate receptor TrkA in PC12 cells. In vivo model, in which NGF was injected into the plantar area of hindpaw in mice, revealed that the addition of F(ab’)2 fragments significantly attenuated the NGF-induced mechanical hypersensitivity induced by NGF injection. Furthermore, the addition of F(ab’)2 fragments also suppressed NGF-induced abnormal sympathetic innervation in the NGF-injected planter skin. These findings suggest that the F(ab’)2 fragment can be a promising candidate for analgesic and painless nerve regeneration therapies.

Free Research Field

麻酔学

Academic Significance and Societal Importance of the Research Achievements

世界的なオピオイドパンデミックなどの諸問題で新規鎮痛薬の開発の必要性が叫ばれる中、神経成長因子(nerve growth factor: NGF)は古くから鎮痛標的として注目されてきた。しかしながら、大きな脚光を浴びた抗NGF抗体治療は、感覚障害や骨破壊の促進などの重篤な副作用の出現により行き詰まりを見せている。これに対し本研究での知見は多彩なNGFの生理作用のなかでより痛みに特異的な経路の選択的阻害により、安全かつ有効な鎮痛薬の開発につながる知見となる。また、痛みを取り除くことでNGFの強力な神経再生作用を活かすことで、安全な神経再生治療への発展も期待できる。