Yan Tingfei, Zhang Fuguo, Sun Chenxi, Sun Jingchuan, Wang Yuan, Xu Ximing, Shi Jiangang, Shi Guodong
Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Department of Spine Surgery, Taizhou First People's Hospital, Taizhou 318020, China.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):506-511. doi: 10.1016/j.bbrc.2017.11.013. Epub 2017 Nov 3.
Previous studies have demonstrated that microRNAs (miRNAs) play important roles in the pathogenesis of neuropathic pain. In the present study, we found that miR-32-5p was significantly upregulated in rats after spinal nerve ligation (SNL), specifically in the spinal microglia of rats with SNL. Functional assays showed that knockdown of miR-32-5p greatly suppressed mechanical allodynia and heat hyperalgesia, and decreased inflammatory cytokine (IL-1β, TNF-α and IL-6) protein expression in rats after SNL. Similarly, miR-32-5p knockdown alleviated cytokine production in lipopolysaccharide (LPS)-treated spinal microglial cells, whereas its overexpression had the opposite effect. Mechanistic investigations revealed Dual-specificity phosphatase 5 (Dusp5) as a direct target of miR-32-5p, which is involved in the miR-32-5p-mediated effects on neuropathic pain and neuroinflammation. We demonstrated for the first time that miR-32-5p promotes neuroinflammation and neuropathic pain development through regulation of Dusp5. Our findings highlight a novel contribution of miR-32-5p to the process of neuropathic pain, and suggest possibilities for the development of novel therapeutic options for neuropathic pain.
先前的研究表明，微小RNA（miRNA）在神经性疼痛的发病机制中起重要作用。在本研究中，我们发现脊髓神经结扎（SNL）后大鼠体内的miR-32-5p显著上调，特别是在SNL大鼠的脊髓小胶质细胞中。功能测定表明，敲低miR-32-5p可显著抑制SNL大鼠的机械性异常性疼痛和热痛觉过敏，并降低炎性细胞因子（IL-1β、TNF-α和IL-6）的蛋白表达。同样，敲低miR-32-5p可减轻脂多糖（LPS）处理的脊髓小胶质细胞中的细胞因子产生，而其过表达则产生相反的效果。机制研究表明双特异性磷酸酶5（Dusp5）是miR-32-5p的直接靶点，其参与了miR-32-5p介导的对神经性疼痛和神经炎症的影响。我们首次证明miR-32-5p通过调节Dusp5促进神经炎症和神经性疼痛的发展。我们的研究结果突出了miR-32-5p在神经性疼痛过程中的新作用，并为开发神经性疼痛的新型治疗方案提供了可能性。
