RUNX1 Induces Central Neuropathic Pain by Activating Microglia and Triggering the Inflammatory Response in Spinal...

Runt-related transcription factor 1 (RUNX1) is a highly conserved transcription factor involved in immune regulation, inflammation, and nociceptive neuron differentiation. However, its role in central neuropathic pain (CNP) induced by SCI remains unclear. Here, we investigated RUNX1 expression after SCI and its impact on CNP. Using scAAV-mediated RUNX1 knockdown in the spinal cord of SCI rats, we assessed nociceptive behaviors of mechanical allodynia and thermal hyperalgesia by hind paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) before injury and at 21-, 35-, and 49-days post-injury. RUNX1 mRNA and protein levels were analyzed via RT-qPCR and Western blotting, while immunohistochemistry was used to examine its distribution. Our findings revealed that RUNX1 expression was significantly elevated in microglia following SCI. RUNX1 knockdown notably increased PWT and PWL as well as a significant decrease in the aberrant sprouting of nociceptive fibers in SCI rats. Furthermore, in lipopolysaccharide (LPS)-treated BV-2 microglia, RUNX1 knockdown markedly reduced microglial activation and inflammation. A similar reduction in microglial activation and neuroinflammation was observed in SCI rats following RUNX1 knockdown. These findings suggest that RUNX1 contributes to CNP after SCI by promoting microglial activation and neuroinflammation, identifying it as a potential therapeutic target for SCI-induced neuropathic pain.