Overexpression Of miR138 Ameliorates Spared Sciatic Nerve Injury-Induced Neuropathic Pain Through The Anti-Inflammatory Response In Mice

Abstract

Benfan Zhu,1,* Jie Gao,1–4,* Yeling Ouyang,3,4 Zhiqiang Hu,3,4 Xiangdong Chen3,4 1Department of Pain, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, People’s Republic of China; 3Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 4Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangdong ChenDepartment of Anesthesiology, Union Hospital, No.1277 Jiefang Avenue, Wuhan, Hubei province 43022, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: The emerging role of inflammation in the initiation and maintenance of neuropathic pain has been confirmed. Previous studies have reported that miR138 has neuroprotective and anti-inflammatory effects in animal models of spinal cord injury and in human coronary artery endothelial cell injury, while its effect on neuropathic pain is still not known. As the mechanism of neuropathic pain remains unclear, we investigated whether miR138 is involved in the development of neuropathic pain and the role of miR138 in the modulation of inflammation in the spinal cord in a mouse model of neuropathic pain induced by spared sciatic nerve injury (SNI).Materials and methods: Firstly, the expression of miR138 in spinal cord was evaluated on days 1, 3, 5, 7, 9 and 14 after SNI. And then, LV-miR-control and LV-miR138 were intrathecally injected 1 week before the surgery followed by investigation of the expression of miR138, mechanical allodynia and thermal hyperalgesia on day 1, 3, 5, 7, 9, 14 after SNI. Ipsilateral L4-L6 spinal cord tissue was harvested on day 14 post-SNI and detected by Western blotting, enzyme-linked immunosorbent assay or immunohischemistry.Results: We observed decreased expression of miR138 and increased expression of proinflammatory cytokines, along with activated microglia, astrocytes and nuclear factor-κВ (NF-κВ), in the spinal cord dorsal horn after SNI. Moreover, the intrathecal upregulation of miR138 significantly alleviated SNI-induced mechanical allodynia and thermal hyperalgesia, downregulated the production of proinflammatory cytokines, and deactivated microglia, astrocytes and NF-κВ.Conclusion: The results indicate that miR138 contributes to the development of neuropathic pain and that the overexpression of miR138 alleviates pain hypersensitivity by inhibiting proinflammatory cytokine production and glial activation, which suggests a novel target for reducing neuropathic pain.Keywords: neuropathic pain, miR138, spared sciatic nerve injury, NF-κ&#x0412

Keywords

• neuropathic pain
• mir138
• spared sciatic nerve injury
• nf-κв