Tracking the water permeability of TRPV1 using upconversion nanoprobes in single live cells. Credit: Nature Biomedical Engineering (2024). DOI: 10.1038/s41551-024-01288-2

Researchers have made a discovery regarding the TRPV1 (transient receptor potential vanilloid 1) ion channel and its role in pain perception. The study reveals how solvent molecules can modulate pain signals, offering a potential pathway for a safer, non-addictive pain management approach.

Pain management is a critical aspect of health care, directly impacting quality of life and overall well-being. The TRPV1 , essential for pain sensing, undergoes pore expansion when activated, allowing ions and larger molecules to pass through. However, the ability of water molecules to permeate the TRPV1 channel has remained uncertain.

To address this, the research team led by Professor Liu Xiaogang from the NUS Department of Chemistry developed an upconversion nanoprobe capable of distinguishing between ordinary water (Hâ‚‚O) and deuterated water (Dâ‚‚O). This advanced technology enabled tracking of water dynamics at both the single-cell and single-molecule levels.

The study showed that when Dâ‚‚O passed through the TRPV1 channel, it suppressed pain signal transmission and achieved effective analgesia. This research was conducted in collaboration with Professor Chao Chang from Peking University and National Innovation Institute of Defense Technology, China, and also with Assistant Professor Bilin Zhuang when she was with Yale-NUS College.

The findings were published in the journal on 21 November 2024.

Simulated Na+ movement through the TRPV1 channel pore under H2O or D2O environments. Credit: Nature Biomedical Engineering (2024). DOI: 10.1038/s41551-024-01288-2

Administering Dâ‚‚O to pre-clinical models, the team successfully reduced both acute and chronic inflammatory pain transmission without affecting other neurological responses. This solvent-mediated analgesia mechanism provides an effective, biocompatible, and non-addictive alternative to traditional pain medications, circumventing issues related to drug dependency and tolerance.

Prof Liu said, "This discovery not only expands the scientific understanding of TRPV1 functionality but also opens new avenues for . The research team aims to further explore the effects of Dâ‚‚O on other ion channels, potentially applying this mechanism to treat neurological conditions and other medical challenges.

"The solvent-mediated analgesia mechanism represents an innovative breakthrough in , potentially driving the development of safer, non-addictive pain therapies for clinical use."

More information: Yuxia Liu et al, Solvent-mediated analgesia via the suppression of water permeation through TRPV1 ion channels, Nature Biomedical Engineering (2024).