Ji Li-Juan, Su Jing, Xu An-Le, Pang Bo, Huang Qiang-Min
Department of Sport Medicine and Rehabilitation Center, School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Department of Rehabilitation, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, China.
J Cell Biochem. 2019 Feb;120(2):1694-1701. doi: 10.1002/jcb.27486. Epub 2018 Sep 6.
Neuropathic pain is a kind of chronic pain because of dysfunctions of somatosensory nerve system. Recently, many studies have demonstrated that microRNAs (miRs) play crucial roles in neuropathic pain development. This study was designed to investigate the effects of miR-134-5p on the process of neuropathic pain progression in a rat model established by chronic sciatic nerve injury (CCI). First, we observed that miR-134-5p was significantly decreased in CCI rat models. Overexpression of miR-134-5p strongly alleviated neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammatory cytokine expression, such as IL-6, IL-1β and TNF-α in CCI rats were greatly repressed by upregulation of miR-134-5p. Twist1 has been widely regarded as a poor prognosis biomarker in diverse diseases. Here, by using bioinformatic analysis, 3'-untranslated region (UTR) of Twist1 was predicted to be a downstream target of miR-134-5p in our study. Here, we found that overexpression of miR-134-5p was able to suppress Twist1 dramatically. Furthermore, it was exhibited that Twist1 was increased in CCI rats time-dependently and Twist1 was inhibited in vivo. Subsequently, downregulation of Twist1 in CCI rats could depress neuropathic pain progression via inhibiting neuroinflammation. In conclusion, our current study indicated that miR-134-5p may inhibit neuropathic pain development through targeting Twist1. Our findings suggested that miR-134-5p might provide a novel therapeutic target for neuropathic pain.
神经性疼痛是一种由于躯体感觉神经系统功能障碍引起的慢性疼痛。最近，许多研究表明，微小RNA（miR）在神经性疼痛的发展中起关键作用。本研究旨在探讨miR-134-5p在慢性坐骨神经损伤（CCI）建立的大鼠模型中对神经性疼痛进展过程的影响。首先，我们观察到在CCI大鼠模型中miR-134-5p显著降低。miR-134-5p的过表达强烈减轻了包括机械性和热性痛觉过敏在内的神经性疼痛行为。同时，miR-134-5p的上调极大地抑制了CCI大鼠中炎性细胞因子如IL-6、IL-1β和TNF-α的表达。Twist1在多种疾病中被广泛认为是一种预后不良的生物标志物。在本研究中，通过生物信息学分析预测Twist1的3'非翻译区（UTR）是miR-134-5p的下游靶点。在这里，我们发现miR-134-5p的过表达能够显著抑制Twist1。此外，结果显示Twist1在CCI大鼠中随时间依赖性增加且在体内受到抑制。随后，CCI大鼠中Twist1的下调可通过抑制神经炎症来抑制神经性疼痛的进展。总之，我们目前的研究表明miR-134-5p可能通过靶向Twist1来抑制神经性疼痛的发展。我们的研究结果表明miR-134-5p可能为神经性疼痛提供一种新的治疗靶点。
