ORIGINAL RESEARCH article
Front. Neurol.
Sec. Headache and Neurogenic Pain
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1641450
This article is part of the Research TopicReviews In: Molecular mechanisms of chronic pain and neuropathic pain pathwaysView all articles
NGF/ERK Signaling-mediated Epigenetic Regulation of Neuropathic Pain in the Cerebrospinal Fluid-contacting Nucleus
Provisionally accepted
Guangling Li1
Chao Wang2*- 1Department of Anesthesiology, Affiliated Hospital of Jiangnan University, Wuxi, China
- 2Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
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ABSTRACT Objective: Neuropathic pain (NP) is a debilitating condition that is associated with multiple molecular alterations in the nervous system. This is the first study to demonstrate the epigenetic regulatory function of nerve growth factor (NGF), mediated through the ERK signaling pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) regarding NP. The objective of this work was to characterize the role of NGF in this specific brain region, including its downstream effects on histone acetylation in the CCI model in the rat. Methods: A rat model of NP was established using CCI. NGF expression and its impact on pain pathways were investigated. NGF levels in the CSF-CN were assessed, and the effects of NGF on neuropathic pain were evaluated by administering NGF antibodies and ERK antagonists. Immunohistochemistry and Western blotting measured key molecular markers, including p-ERK, THMA, and acetylated histone H3K56. Statistical analysis was performed with significance set at p < 0.05. Results: CCI induced significant upregulation of NGF in the CSF-CN. Treatment with NGF antibodies alleviated NP symptoms and reduced p-ERK levels in the CSF-CN. ERK antagonists further diminished THMA and decreased acetylated histone H3K56 expression. Conclusion: We are the first study to identify an NGF/ERK/Ac-H3 signaling axis in the CSF-CN as a central mediator in neuropathic pain via epigenetic modulation. Our results suggest that targeting this novel signaling pathway may provide new therapeutic options to manage NP.
Keywords: CSF-cN, NGF, ERK1/2, Acetylated histone, neuropathic pain, CCI
Received: 05 Jun 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chao Wang, winnerwang0206@126.com
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