Abstract
Background
Voltage-gated sodium channels (VGSCs) are essential for generating and propagating action potentials in excitable cells. They are considered to be promising potential targets for analgesics acting on nociceptive neurons. However, the translation of animal model analgesic data to humans makes VGSCs-targeting analgesic drug development challenging. Starting with human experience to find analgesics can reduce such failures. Traditional Chinese medicine (TCM), a traditional medical system, has rich human experience of analgesics, which means many Traditional Chinese Medicine Herbs (TCMH) are worth exploring for analgesic drug development. However, studies of the analgesic mechanisms of TCMH need to be conducted at the cellular and molecular level for a VGSC perspective.
Purpose
In this review, we provide an overview of the TCMH analgesics and molecules from TCMH, that act on VGSCs, especially subtype Nav1.3, Nav1.7, and Nav1.8, along with a brief discussion on pharmaceutical potential for pain management. We also provide references for Chinese medicine to study pain relief mechanisms at the molecular level of sodium ion channels.
Methods
Using Web of Science, the PubMed, and China National Knowledge Infrastructure databases, we conducted a comprehensive search of literature and data on TCMH and VGSCs published before October 2024.
Conclusion
While Navl.3, Navl.7, Navl.8 and Navl.9 are involved in the development and maintenance of pain, Navl.8 can be studied as a potential drug target. The traditional Chinese medicine herbs involved sodium ion channels are primarily categorized into seven types, including 30 well-defined natural ingredients and 33 TCMH extracts. Studying the interactions between the components of TCMH is an important prerequisite for further exploration of how a specific analgesic TCM or TCM formula modulates ion channels or whether it binds to specific sites on these channels.
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- AGAP:
-
Antitumor–analgesic peptide
- Amm:
-
Androctonus mauretanicus mauretanicus
- ANEP:
-
Anti-neuroexcitation peptide
- BLA:
-
Bulleyaconitine A
- GJG:
-
Goshajinkigan
- HNTX-IV:
-
Hainantoxin-IV
- HWTX-IV:
-
Huwentoxin-IV
- JZTX-34:
-
Jingzhaotoxin-34
- LCA:
-
Licochalcone A
- MkTx-3:
-
Makatoxin-3
- NSAIDs:
-
Non-steroidal anti-inflammatory drugs
- PA:
-
Processed aconite root
- PDPN:
-
Painful diabetic peripheral neuropathy
- ProTxII:
-
Protoxin-II
- RJ-III:
-
Rhodojaponin III
- SNI:
-
Spared nerve injury
- Ssm6a:
-
µ-SLPTX-Ssm6a
- TCM:
-
Traditional Chinese medicine
- TCMH:
-
Traditional Chinese medicine herbs
- TTX:
-
Tetrodotoxin
- TTX-R:
-
Tetrodotoxin-resistance
- TTX-S:
-
Tetrodotoxin-sensitive
- VGSCs:
-
Voltage-gated sodium channels
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Acknowledgements
The authors thank Cancer Research UK for support., thank the Sichuan Province science and technology Department Sichuan Province science and technology plan project (No. 2024NSFSC0712, No. 2021YJ0251), the Science and technology project of Sichuan Provincial Health Commission (No. 24QNMP011), Science and technology research project of Sichuan Administration of Traditional Chinese Medicine (No. 2023MS600), Chengdu University of Traditional Chinese Medicine Xinglin scholars Qingji talent project (No. QJRC2022027) and the fellowship from China Scholarship Council (No. 202308510149) for their financial support. The authors also thank thesupport of the experimental equipments from the State Key Laboratory of CDUTCM and Wolfson Institute for Biomedical Research of UCL.
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Zhen Zhang & John N. Wood conceived the work. Zhen Zhang: Writing – review & editing, Writing – original draft, Project administration & Funding acquisition. Fuyu Xie: Writing – review & editing, Software, Formal analysis. Yue Zhang: Writing – review & editing, Data curation, Validation. Mengxia Wu: Investigation & Validation. John N. Wood: Writing – review & editing, Project administration & Funding acquisition. Ahmed.M.M. Mahmoud: Review & editing.
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Zhang, Z., Xie, FY., Zhang, Y. et al. Traditional Chinese medicine and natural small molecules for pain treatment via voltage-gated sodium channels: a review. Phytochem Rev (2025). https://doi.org/10.1007/s11101-025-10151-4
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DOI: https://doi.org/10.1007/s11101-025-10151-4