Crosstalk between HCN channels and hydrogen sulfide in the generation of neuropathic pain.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09254
• 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: Iwate Medical University
• Principal Investigator: Komagiri You 岩手医科大学, 医学部, 助教 (80405753)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 硫化水素 / HCNチャネル / 後根神経節 / 一酸化窒素 / 神経因性疼痛

Outline of Final Research Achievements

I investigated the crosstalk between hydrogen sulfide and hyperpolarization-activated cation channels (HCN channels), which have been suggested to contribute to the pathogenesis of neuropathic pain. Using electrophysiological recording and fluorescence imaging, I revealed a novel channel regulation mechanism in which hydrogen sulfide enhances nitric oxide production and activates HCN channels via guanylate cyclase in cultured dorsal root ganglion neurons. Furthermore, hydrogen sulfide enhanced the recovery phase of the membrane potential from hyperpolarizing stimulation. This study suggests the possibility that hydrogen sulfide modulates the excitability of dorsal root ganglion neurons via HCN channel activation.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

本研究成果によって硫化水素が一酸化窒素産生を介してHCNチャネルを活性化させ、後根神経節細胞の興奮性を上昇させる可能性が示唆された。硫化水素とHCNチャネルはこれまで神経因性疼痛における後根神経節細胞の異常発火メカニズムへの関与が別個に報告されてきた。本研究によりこの２つの分子の連関が明らかになったことから、神経因性疼痛の病態発現メカニズムのさらなる解明や効果的な治療法の確立につながる可能性がある。