Research Paper Volume 12, Issue 11 pp 11004—11024
Upregulation of Mlxipl induced by cJun in the spinal dorsal horn after peripheral nerve injury counteracts mechanical allodynia by inhibiting neuroinflammation
- 1 Department of Rehabilitation, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
- 2 Department of Rehabilitation, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong Province, China
- 3 Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong Province, China
- 4 Department of Rehabilitation, Shenzhen University General Hospital, Shenzhen 518055, China
Received: January 27, 2020 Accepted: April 28, 2020 Published: June 9, 2020https://doi.org/10.18632/aging.103313
How to Cite
Copyright © 2020 Zhan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Mlxipl regulates glucose metabolism, lipogenesis and tumorigenesis and has a wide-ranging impact on human health and disease. However, the role of Mlxipl in neuropathic pain remains unknown. In this study, we found that Mlxipl was increased in the ipsilateral L4–L6 spinal dorsal horn after Spared Nerve Injury surgery. Knockdown of Mlxipl in the ipsilateral L4–L6 spinal dorsal horn by intraspinal microinjection aggravated Spared Nerve Injury-induced mechanical allodynia and inflammation in the spinal dorsal horn, on the contrary, overexpression of Mlxipl inhibited mechanical allodynia and inflammation. Subsequently, the rat Mlxipl promoter was analyzed using bioinformatics methods to predict the upstream transcription factor cJun. Luciferase assays and ChIP-qPCR confirmed that cJun bound to the promoter of Mlxipl and enhanced its expression. Finally, we demonstrated that Mlxipl inhibited the inflammatory responses of lipopolysaccharide-induced microglia and that Mlxipl was regulated by the transcription factor cJun. These findings suggested that cJun-induced Mlxipl upregulation in the spinal dorsal horn after peripheral nerve injury provided a protective mechanism for the development and progression of neuropathic pain by inhibiting microglial-derived neuroinflammation. Targeting Mlxipl in the spinal dorsal horn might represent an effective strategy for the treatment of neuropathic pain.
SNI: Spared Nerve Injury; 50% PWT: 50% Paw Withdrawal Threshold; SDH: Spinal Dorsal Horn; LPS: Lipopolysaccharide; BL: Baseline; Ipsi: Ipsilateral; Contra: Contralateral.