Elucidation of pathological mechanism of congenital insensitivity to pain with loss of Nav1.7 function for the development of new analgesics and analgesic methods

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08938
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Horishita Takafumi 産業医科大学, 医学部, 教授 (40369070)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 慢性疼痛 / 電位依存性ナトリウムチャネル / 先天性無痛症 / 機能喪失型Nav1.7 / 局所麻酔作用

Outline of Final Research Achievements

In order to contribute to the development of new analgesics and analgesic methods for chronic pain, we set up a research plan to elucidate the pathogenesis of congenital insensitivity to pain patients at the molecular level. However, it was difficult to functionally co-express wild-type Nav1.7 and pain receptors, and we could not obtain functional analysis. Therefore, we investigated electrophysiologically the effects of neferine, a benzylisoquinoline alkaloid, a component of lotus juvenile buds, a Chinese herb with various physiological effects, on the Nav α subunit expressed in the nervous system. We found that neferine inhibits Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 functions in a concentration-dependent manner, indicating its potential as a new local anesthetic.

Free Research Field

麻酔科学、疼痛関連

Academic Significance and Societal Importance of the Research Achievements

神経障害性疼痛や侵害受容性疼痛を成因とする慢性疼痛は、既存の鎮痛薬では治療困難な例が多く、新たな鎮痛薬の開発が進められているが、有効な薬物の開発には至っていない。電位依存性ナトリウムチャネル（Nav）は慢性疼痛発生機序に重要な役割を持っており、ネフェリンが神経系に発現するNavαサブユニット機能を抑制するという本研究の成果は、新たな鎮痛薬としての可能性を示している。さらに、ネフェリンは従来の局所麻酔薬とは異なる作用機序を持つことが示されており、この新たな抑制機構はNavをターゲットにした新たな鎮痛薬・鎮痛法開発への有用な手がかりになることが期待される。