A synthetic peptide, derived from neurotoxin GsMTx4, acts as a non-opioid analgesic to alleviate mechanical and neuropathic pain through the TRPV4 channel

https://doi.org/10.1016/j.apsb.2024.12.028

This new article publication from Acta Pharmaceutica Sinica B, discusses how A synthetic peptide, derived from neurotoxin GsMTx4, acts as a non-opioid analgesic to alleviate mechanical and neuropathic pain through the TRPV4 channel.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, the authors of this article demonstrated that a GsMTx4-based 17-residue peptide, which they call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. This study identified a potential drug for curing mechanical pain and exposed its mechanism.

Keywords: Peptide; Pain; Non-opioid analgesic; Mechanical pain; TRPV4; Tolerance addiction; Mechanosensitive channel

Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383524004854-ga1_lrg.jpg

A natural toxin-based-peptide P10581 is discovered to selectively alleviate mechanical hyperalgesia through TRPV4 channel which can be as strong as morphine without any side effects like morphine.

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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.

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CiteScore: 22.4

Impact Factor: 14.8 (Top 5 journal in the category of Pharmacology and pharmacy)

JIF without self-citation: 13.9

ISSN 2211-3835

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ShaoXi Ke, Ping Dong, Yi Mei, JiaQi Wang, Mingxi Tang, Wanxin Su, JingJing Wang, Chen Chen, Xiaohui Wang, JunWei Ji, XinRan Zhuang, ShuangShuang Yang, Yun Zhang, Linda M. Boland, Meng Cui, Masahiro Sokabe, Zhe Zhang, QiongYao Tang, A synthetic peptide, derived from neurotoxin GsMTx4, acts as a non-opioid analgesic to alleviate mechanical and neuropathic pain through the TRPV4 channel, Acta Pharmaceutica Sinica B, Volume 15, Issue 3, 2025, Pages 1447-1462, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2024.12.028.