Activation of the ion channel transient receptor potential vanilloid 1 (TRPV1), which is integral to pain perception, leads to an expansion of channel width, facilitating the passage of cations and large organic molecules. However, the permeability of TRPV1 channels to water remains uncertain, owing to a lack of suitable tools to study water dynamics. Here, using upconversion nanophosphors to discriminate between H₂O and D₂O, by monitoring water permeability across activated TRPV1 at the single-cell and single-molecule levels, and by combining single-channel current measurements with molecular dynamics simulations, we show that water molecules flow through TRPV1 and reveal a direct connection between water migration, cation flow and TRPV1 functionality. We also show in mouse models of acute or chronic inflammatory pain that the administration of deuterated water suppresses TRPV1 activity, interrupts the transmission of pain signals and mitigates pain without impacting other neurological responses. Solvent-mediated analgesia may inspire alternative options for pain management.

离子通道瞬时受体电位香草酸 1 （TRPV1） 的激活是疼痛感知不可或缺的一部分，导致通道宽度扩大，促进阳离子和有机大分子的通过。然而，由于缺乏研究水动力学的合适工具，TRPV1 通道对水的渗透性仍不确定。在这里，使用上转换纳米荧光粉来区分 H₂O 和 D₂O，通过在单细胞和单分子水平监测活化 TRPV1 的透水性，并将单通道电流测量与分子动力学模拟相结合，我们展示了水分子流经 TRPV1，并揭示了水迁移、阳离子流和 TRPV1 功能之间的直接联系。我们还在急性或慢性炎症性疼痛的小鼠模型中表明，氘水的给药抑制了 TRPV1 活性，中断了疼痛信号的传递并减轻了疼痛，而不会影响其他神经系统反应。溶剂介导的镇痛可能会激发疼痛管理的替代选择。