MicroRNA-7a ameliorates neuropathic pain in a rat model of spinal nerve ligation via the neurofilament light polypeptide-dependent signal transducer and activator of transcription signaling pathway

摘要

Neuropathic pain is a type of chronic pain induced by either central or peripheral nerve injury. MicroRNAs (miRs) 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 (SNL) rat model. After establishment of SNL rat models, rats were infected with adeno associated virus (AAV)-neurofilament light polypeptide (NEFL), AAV-miR-7a or treated with metformin. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed afterward, and the expression of miR-7a and NEFL as well as their interaction was determined. Subsequently, miR-7a was overexpressed or silenced in dorsal root ganglion (DRG) cells to investigate the role of miR-7a in neuropathic pain. Furthermore, the regulatory effect of NEFL on neuropathic pain was detected using plasmid overexpressing NEFL. SNL rat model exhibited upregulation of NEFL but downregulation of miR-7a. Additionally, NEFL accumulation or miR-7a inhibition decreased PWT and PWL. Then, NEFL accumulation or miR-7a inhibition was observed to increase the phosphorylation level of STAT3. miR-7a was found to directly target NEFL and downregulate NEFL. In addition, inhibiting the STAT3 signaling pathway was also revealed to increase PWT and PWL. Collectively, our study demonstrated that miR-7a ameliorated neuropathic pain via blocking the STAT3 signaling pathway by repressing NEFL. These findings, if taken further, can be of important clinical significance in treating patients with neuropathic pain.