Yan Xue-Tao, Ji Li-Juan, Wang Zhiyu, Wu Xingjun, Wang Quan, Sun Shujie, Lu Jing-Min, Zhang Yang
Department of Anesthesiology, Shenzhen Bao'an Maternity and Child Health Hospital, Shenzhen, 518100, China.
Department of Sport Medicine and Pain Clinic, Center of Sports Rehabilitation, School of Sport Science, Shanghai University of Sport, Shanghai, 200438, China.
Int Immunopharmacol. 2017 May;46:156-162. doi: 10.1016/j.intimp.2017.01.027. Epub 2017 Mar 8.
Emerging evidence suggests that microRNAs (miRNAs) play a critical role in the pathogenesis of neuropathic pain. However, the exact role of miRNAs in regulating neuropathic pain remains largely unknown. In this study, we aimed to investigate the potential role of miR-93 in a rat model of neuropathic pain induced by chronic constriction sciatic nerve injury (CCI). We found a significant decrease of miR-93 in the spinal cord of CCI rats compared with sham rats. Overexpression of miR-93 significantly alleviated neuropathic pain development and reduced inflammatory cytokine expression, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 in CCI rats. By bioinformatic analysis and dual-luciferase reporter assay, we found that miR-93 directly targeted the 3'-untranslated region (UTR) of signal transducer and activator of transcription 3 (STAT3), an important regulator of inflammation. Overexpression of miR-93 markedly suppressed the expression of STAT3 in vitro and in vivo. Furthermore, overexpression of STAT3 significantly reversed the miR-93 overexpression-induced suppressive effects on neuropathic pain development and neuroinflammation. Taken together, our study suggests that miR-93 inhibits neuropathic pain development of CCI rats possibly through inhibiting STAT3-mediated neuroinflammation. Our findings indicate that miR-93 may serve as a novel therapeutic target for neuropathic pain intervention.
新出现的证据表明，微小RNA（miRNA）在神经性疼痛的发病机制中起关键作用。然而，miRNA在调节神经性疼痛中的确切作用仍 largely unknown。在本研究中，我们旨在研究miR-93在慢性压迫性坐骨神经损伤（CCI）诱导的神经性疼痛大鼠模型中的潜在作用。我们发现，与假手术大鼠相比，CCI大鼠脊髓中miR-93显著降低。miR-93的过表达显著减轻了神经性疼痛的发展，并降低了炎症细胞因子的表达，包括CCI大鼠中的白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α和IL-6。通过生物信息学分析和双荧光素酶报告基因测定，我们发现miR-93直接靶向信号转导和转录激活因子3（STAT3）的3'非翻译区（UTR），STAT3是炎症的重要调节因子。miR-93的过表达在体外和体内均显著抑制了STAT3的表达。此外，STAT3的过表达显著逆转了miR-93过表达诱导的对神经性疼痛发展和神经炎症的抑制作用。综上所述，我们的研究表明，miR-93可能通过抑制STAT3介导的神经炎症来抑制CCI大鼠的神经性疼痛发展。我们的研究结果表明，miR-93可能作为神经性疼痛干预的新治疗靶点。
