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, we demonstrated that a GsMTx4-based 17-residue peptide, which we 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 <i>μ</i>-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 <i>Trpv4</i> knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

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Publication Details

Journal
Acta Pharmaceutica Sinica B
Published
2024-12-30
DOI
https://doi.org/10.1016/j.apsb.2024.12.028
Citations
3
Primary Topic
Pain Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
0.98

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article

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

Qiong‐Yao Tang, Ping Dong, Yunqing Mei, Yun Zhang et al.
3 citations
Acta Pharmaceutica Sinica B
Pain Mechanisms and Treatments
0.98
article

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

Qiong‐Yao Tang, Ping Dong, Yunqing Mei, Yun Zhang, Linda M. Boland, Masahiro Sokabe, Shao-Xi Ke, Meng Cui, J Wang, Xiaohui Wang, Chen Chen, Jingjing Wang, Zhe Zhang, Shuangshuang Yang, Mingxi Tang, Xin-Ran ZHuang, Wan-xin Su, Junwei Ji
article en
3 citations

Abstract

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, we demonstrated that a GsMTx4-based 17-residue peptide, which we 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 <i>μ</i>-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 <i>Trpv4</i> knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Acta Pharmaceutica Sinica BVol. 15(3)
Kanazawa Institute of Technology (JP), Northeastern University (US), University of Richmond (US), Xuzhou Medical College (CN), Ruijin Hospital (CN), Affiliated Hospital of Southwest Medical University (CN), Yan'an University (CN), Second Affiliated Hospital of Zhejiang University (CN), Nagoya University (JP)
National Natural Science Foundation of China, Zhejiang University, Southwest Medical University, Luzhou Science and Technology Bureau
Good health and well-being
Openalex Percentile: Top 22%
Pain Mechanisms and Treatments
0.98
DOIOpen Access PDFOpenAlex
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