Endothelin-Converting Enzyme-Like 1 Regulated by LIF Contributes to Chronic Constriction Injury-Induced Neuropathic Pain in Mice

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-09-04 DOI:10.1111/cns.70578

Feng Gao, Yuchen Pan, Yong Huang, Chen Gu, Xiaowei Song, Cunjin Wang

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Abstract

Aims

This study is to investigate the role of Endothelin-converting enzyme-like 1 (ECEL1) in neuropathic pain (NP).

Methods

The expression of ECEL1 was modulated by injecting adeno-associated virus 5 (AAV5) carrying Ecel1 shRNA or full-length Ecel1 into the dorsal root ganglion (DRG) of mice with a chronic constriction injury (CCI) model. Then, various nociceptive responses were evaluated. Additionally, leukemia inhibitory factor (LIF) was intrathecally injected, or its function was blocked, to observe the changes in ECEL1 expression.

Results

Our findings demonstrate that downregulating ECEL1 expression alleviates CCI-induced pain and reduces the hyperexcitability of injured DRG neurons, which is achieved by inhibiting sympathetic sprouting in the DRG. Conversely, overexpressing ECEL1 in DRG neurons leads to pain hypersensitivity. Additionally, we observed that LIF upregulated ECEL1 expression, while blocking LIF reduced ECEL1 expression and mitigated CCI-induced nociception in mice.

Conclusion

ECEL1 promotes hyperalgesia following CCI and is regulated by LIF, suggesting it could be a new target for NP treatment.

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LIF调控的内皮素转换酶样1参与小鼠慢性收缩性损伤引起的神经性疼痛

目的探讨内皮素转换酶样1 （ECEL1）在神经性疼痛（NP）中的作用。方法将携带ECEL1 shRNA或全长ECEL1的腺相关病毒5 （AAV5）注入慢性收缩性损伤（CCI）模型小鼠背根神经节（DRG），调节ECEL1的表达。然后，评估各种伤害性反应。另外，在鞘内注射白血病抑制因子（leukemia inhibitory factor， LIF）或阻断其功能，观察ECEL1表达的变化。结果下调ECEL1表达可减轻cci诱导的疼痛，降低受损DRG神经元的高兴奋性，这可能是通过抑制DRG的交感神经萌发来实现的。相反，在DRG神经元中过表达ECEL1会导致疼痛超敏反应。此外，我们观察到LIF上调了ECEL1的表达，而阻断LIF则降低了ECEL1的表达并减轻了cci诱导的小鼠伤害感受。结论ECEL1促进CCI后痛觉过敏，并受LIF调节，可能成为NP治疗的新靶点。

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

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.