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

Neuroreport. 2021 Jan 13;32(2):135-143. doi: 10.1097/WNR.0000000000001573.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: MiR-130a-5p inactivated astrocytes by targeting CXCL12/CXCR4, thus alleviating SCI-induced neuropathic pain.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Behavior, Animal
  • Chemokine CXCL12 / metabolism*
  • Down-Regulation
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neuralgia / etiology
  • Neuralgia / genetics*
  • Neuralgia / metabolism
  • Neuralgia / physiopathology
  • Pain Measurement
  • Real-Time Polymerase Chain Reaction
  • Receptors, CXCR4 / metabolism*
  • Spinal Cord Injuries / complications
  • Up-Regulation

Substances

  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • MIRN130 microRNA, mouse
  • MicroRNAs
  • Receptors, CXCR4