Utidelone induces mechanical and cold allodynia in mice via TRPA1 activation.

IF 2.8 3区医学 Q2 NEUROSCIENCES

Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-08-28 DOI:10.1177/17448069251377633

Wenwen Gao, Cunjin Su, Liya Dai, Jialong Tao, Yusong Zhang

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引用次数: 0

Abstract

Objective: Utidelone (UTD1), a recently approved epothilones analog in China for metastatic breast cancer, is endorsed in combination with capecitabine for metastatic breast cancer patients who have encountered first-line therapy failures. Despite its clinically verified therapeutic efficacy, it is concurrently associated with peripheral neuropathic pain, particularly affecting extremities. However, the etiology of UTD1-induced peripheral neuropathic pain remains unclear.

Methods: The present investigation built a mouse pain model induced by UTD1, resulting in marked mechanical and cold allodynia.

Results: Examination of the dorsal root ganglia unveiled a notable upregulation of TRPA1, accompanied by noteworthy alterations in oxidative stress-related markers, including ATF4, SOD2, CAT, and Cyt-C. The TRPA1 antagonist HC-030031, resulted in the alleviation of mechanical and cold allodynia in the UTD1-induced pain model, as well as two antioxidants, including Mito-tempo and edaravone.

Interpretation: The present study will provide new strategies for pain relieving induced by UTD1.

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EXPRESS：优替龙通过激活TRPA1诱导小鼠机械和冷性异常痛。

优替龙（UTD1）是最近在中国被批准用于治疗转移性乳腺癌的一种艾替龙类似物，被推荐与卡培他滨联合用于对一线治疗无反应的患者。虽然其治疗效果已被临床证实，但它也与周围神经性疼痛有关，主要发生在四肢。然而，utd1诱导的周围神经性疼痛的发病机制仍然难以捉摸。本研究建立了UTD1致痛小鼠模型，引起明显的机械和冷性异常痛。对背根神经节的分析显示，TRPA1显著上调，氧化应激标志物如ATF4、SOD2、CAT和Cyt-C也发生了显著变化。TRPA1拮抗剂HC-030031和两种抗氧化剂Mito-tempo和依达拉奉均可显著缓解utd1诱导的疼痛模型中的机械性和冷性异常痛。本研究提出了减轻UTD1引起的疼痛的新方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Pain 医学-神经科学

CiteScore

5.60

自引率

3.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.