Evaluation of sodium channel function associated with congenital insensitivity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16443
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Shinshu University
• Principal Investigator: Kiyosawa Kenkichi 信州大学, 医学部附属病院, 助教(特定雇用) (50624772)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 電位依存性ナトリウムチャネル / 先天性無痛症

Outline of Final Research Achievements

We analyzed the function of the mutant NaV1.7 channel in patients with congenital insensitivity of pain. NaV1.7 channel function analysis was performed using the patch clamp method. It was confirmed the average peak current density of mutation channels was significantly smaller than Wild-Type channels, and the current-voltage relationship of mutation channels showed a tendency to shift slightly to the right of WT current-voltage relationship.
We evaluated the behavioral experiment with NaV1.7 mutant mice. For testing mechanical responses, calibrated von Frey filaments were applied．The response to mechanical noxious stimuli was found to be diminished. We also isolated the dorsal root ganglion from this mutant mouse and attempted to evaluate its electrophysiological function, but it was not measured within the study period.

Free Research Field

麻酔

Academic Significance and Societal Importance of the Research Achievements

医療者および急性・慢性痛患者に とって，より安全により痛みだけを除ける理想的な鎮痛薬の開発が期待されている．我々は，痛み刺激に対する感受性が欠失しているという先天性無痛症患者に出会った．本症例は電位依存性ナトリウムチャネルの変異が関与していた．この変異ナトリウムチャネルの解析を行うことで，局所麻酔薬に代表されるナトリウムチャネル阻害薬の新規ターゲットととなるタンパク部位が同定できれば，理想的な鎮痛薬の開発の一助となりうる．