2. Academic Validation
  3. Solvent-mediated analgesia via the suppression of water permeation through TRPV1 ion channels

Solvent-mediated analgesia via the suppression of water permeation through TRPV1 ion channels

  • Nat Biomed Eng. 2024 Nov 21. doi: 10.1038/s41551-024-01288-2.
Yuxia Liu # 1 2,  Yuanyuan He # 3 4 5,  Jiahuan Tong # 6,  Shengyang Guo 7 8,  Xinyu Zhang 7 8,  Zichao Luo 1 2,  Linlin Sun 7 8,  Chao Chang 9 10,  Bilin Zhuang 11,  Xiaogang Liu 12 13
Affiliations

Affiliations

  • 1 Department of Chemistry, National University of Singapore, Singapore, Singapore.
  • 2 The N.1 Institute for Health, National University of Singapore, Singapore, Singapore.
  • 3 School of Physics, Peking University, Beijing, China.
  • 4 Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing, China.
  • 5 School of Safety Engineering, North China Institute of Science and Technology, Hebei, China.
  • 6 Yale-NUS College, National University of Singapore, Singapore, Singapore.
  • 7 Department of Neurobiology, School of Basic Medicine, Peking University, Beijing, China.
  • 8 Key Laboratory for Neuroscience of Ministry of Education and National Health Commission of China, Beijing, China.
  • 9 School of Physics, Peking University, Beijing, China. gwyzlzssb@pku.edu.cn.
  • 10 Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing, China. gwyzlzssb@pku.edu.cn.
  • 11 Yale-NUS College, National University of Singapore, Singapore, Singapore. bzhuang@g.hmc.edu.
  • 12 Department of Chemistry, National University of Singapore, Singapore, Singapore. chmlx@nus.edu.sg.
  • 13 The N.1 Institute for Health, National University of Singapore, Singapore, Singapore. chmlx@nus.edu.sg.
  • # Contributed equally.
PMID: 39572786 DOI: 10.1038/s41551-024-01288-2
Abstract

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.

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