1 Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, P.R. China.
2 Department of Anesthesiology, the First Affiliated Hospital of University of South China, Hengyang, P.R. China.
Mol Pain. 2019 Jan-Dec;15:1744806919842464. doi: 10.1177/1744806919842464.
Neuropathic pain is a type of chronic pain induced by either central or peripheral nerve injury. MicroRNAs have been recently linked to many diseases, including neuropathic pain. However, the role of miR-7a in neuropathic pain still remains elusive. Thus, we aim to investigate the effects of miR-7a on neuropathic pain based on the spinal nerve ligation rat model. After establishment of spinal nerve ligation rat models, rats were infected with adeno-associated virus-neurofilament light polypeptide, adeno-associated virus-miR-7a or treated with metformin. The paw withdrawal threshold and paw withdrawal latency were assessed afterward, and the expression of miR-7a and neurofilament light polypeptide as well as their interaction was determined. Subsequently, miR-7a was overexpressed or silenced in dorsal root ganglion cells to investigate the role of miR-7a in neuropathic pain. Furthermore, the regulatory effect of neurofilament light polypeptide on neuropathic pain was detected using plasmid overexpressing neurofilament light polypeptide. Spinal nerve ligation rat model exhibited upregulation of neurofilament light polypeptide but downregulation of miR-7a. In addition, neurofilament light polypeptide accumulation or miR-7a inhibition decreased paw withdrawal threshold and paw withdrawal latency. Then, neurofilament light polypeptide accumulation or miR-7a inhibition was observed to increase the phosphorylation level of signal transducer and activator of transcription. miR-7a was found to directly target neurofilament light polypeptide and downregulate neurofilament light polypeptide. In addition, inhibiting the signal transducer and activator of transcription signaling pathway was also revealed to increase paw withdrawal threshold and paw withdrawal latency. Collectively, our study demonstrated that miR-7a ameliorated neuropathic pain via blocking the signal transducer and activator of transcription signaling pathway by repressing neurofilament light polypeptide. These findings, if taken further, can be of important clinical significance in treating patients with neuropathic pain.
神经病理性疼痛是由中枢或外周神经损伤引起的一种慢性疼痛。miRNA 最近与许多疾病有关，包括神经病理性疼痛。然而，miR-7a 在神经病理性疼痛中的作用仍然难以捉摸。因此，我们旨在基于脊神经结扎大鼠模型研究 miR-7a 对神经病理性疼痛的影响。建立脊神经结扎大鼠模型后，用腺相关病毒-神经丝轻链、腺相关病毒-miR-7a 感染大鼠或用二甲双胍治疗。然后评估大鼠的足底退缩阈值和足底退缩潜伏期，并测定 miR-7a 和神经丝轻链的表达及其相互作用。随后，在背根神经节细胞中转染 miR-7a 过表达或沉默，以研究 miR-7a 在神经病理性疼痛中的作用。此外，通过过表达神经丝轻链质粒检测神经丝轻链对神经病理性疼痛的调节作用。脊神经结扎大鼠模型中神经丝轻链表达上调，miR-7a 表达下调。此外，神经丝轻链积累或 miR-7a 抑制降低了足底退缩阈值和潜伏期。然后，观察到神经丝轻链积累或 miR-7a 抑制增加了信号转导和转录激活因子的磷酸化水平。发现 miR-7a 可以直接靶向神经丝轻链并下调神经丝轻链。此外，抑制信号转导和转录激活因子信号通路也增加了足底退缩阈值和潜伏期。综上所述，我们的研究表明，miR-7a 通过抑制信号转导和转录激活因子信号通路来减轻神经病理性疼痛，该通路通过抑制神经丝轻链发挥作用。如果进一步研究这些发现，对于治疗神经病理性疼痛患者可能具有重要的临床意义。
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