Work

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

Year: 2025

Type: article

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.

Source: CNS Neuroscience & Therapeutics

DOI: 10.1111/cns.70578

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