Upregulating miR-130a-5p relieves astrocyte over activation-induced neuropathic pain through targeting C-X-C motif chemokine receptor 12/C-X-C motif chemokine receptor 4 axis.

Abstract

This study intends to explore the role and specific mechanism of miR-130a-5p in neuropathic pain through regulating the C-X-C motif chemokine receptor 12 (CXCL12)-C-X-C motif chemokine receptor 4 (CXCR4) pathway. First, mouse neuropathic pain model was constructed by spinal nerve ligation. MiR-130a-5p mimics were used to upregulate miR-130a-5p in vivo. The behaviour and pain scores of the spinal cord injury (SCI) mice were assessed. In addition, astrocytic activation as well as inflammatory response in the spinal lesions was determined. The results manifested miR-130a-5p was notably downregulated in neuropathic pain model and reached the lowest point at 3 days after injury. Besides, tail vein injection of miR-130a-5p mimics inhibited the activation and inflammatory response of astrocytes, thus alleviating chronic constriction injury-induced neuropathic pain. Moreover, miR-130a-5p inactivated CXCR4 and its downstream Rac1, nuclear factor-κB (NF-κB) and extracellular regulated protein kinases signalling pathways by attenuating CXCL12. MiR-130a-5p inactivated astrocytes by targeting CXCL12/CXCR4, thus alleviating SCI-induced neuropathic pain.