Increased EZH2 Levels in Anterior Cingulate Cortex Microglia Aggravate Neuropathic Pain by Inhibiting Autophagy Following Brachial Plexus Avulsion in Rats.
10.1007/s12264-020-00502-w
- Author:
Xiang-Lei MENG
1
;
Pengfei FU
2
;
Lin WANG
3
;
Xun YANG
1
;
Guanghui HONG
1
;
Xin ZHAO
1
;
Jie LAO
4
Author Information
1. Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
3. Health Management Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, China.
4. Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China. laojiefd@sina.com.
- Publication Type:Journal Article
- Keywords:
Autophagy;
Brachial plexus avulsion;
EZH2;
Neuroinflammation;
Neuropathic pain
- From:
Neuroscience Bulletin
2020;36(7):793-805
- CountryChina
- Language:English
-
Abstract:
After brachial plexus avulsion (BPA), microglia induce inflammation, initiating and maintaining neuropathic pain. EZH2 (enhancer of zeste homolog 2) has been implicated in inflammation and neuropathic pain, but the mechanisms by which it regulates neuropathic pain remain unclear. Here, we found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) secretion in vivo. In rats with BPA-induced neuropathic pain, mechanical and cold hypersensitivities were induced by EZH2 upregulation and inhibited by EZH2 downregulation in the anterior cingulate cortex. Microglial autophagy was also significantly inhibited, with EZH2 inhibition activating autophagy and reducing neuroinflammation in vivo. However, this effect was impaired by inhibiting autophagy with 3-methyladenine, suggesting that the MTOR signaling pathway is a functional target of EZH2. These data suggest that EZH2 regulates neuroinflammation and neuropathic pain via a novel MTOR-mediated autophagy signaling pathway, providing a promising approach for managing neuropathic pain.
