Transcription factor RUNX2 participates in astrocyte-mediated neuropathic pain via transcriptional activation of Ccl2.

Neuroinflammation, which is characterized by glial cell activation and the release of inflammatory factors, is critical for the progression of neuropathic pain. The excessive accumulation of reactive oxygen species (ROS) is related to increased neuroinflammation. Runt-related transcription factor 2 (RUNX2), a regulator of various biological processes, has been reported to regulate the inflammatory response. However, whether RUNX2 participates in neuroinflammation by affecting ROS production remains unclear. In the present study, we investigated the expression pattern of RUNX2 in the context of neuropathic pain induced by chronic compression of the dorsal root ganglion (CCD) and the role of RUNX2 in the development of neuropathic pain. During neuropathic pain, RUNX2 expression was significantly increased in the spinal cord and was mainly localized to astrocytes. Knockdown of RUNX2 attenuated the astrocyte activation and the production of ROS and inflammatory factors induced by CCD surgery, thus relieving neuropathic pain. C-C motif chemokine ligand 2 (CCL2) has been reported to increase ROS generation, thus promoting the inflammatory response. We discovered that RUNX2 transcriptionally activated the expression of Ccl2 by binding to its promoter and that RUNX2 knockdown may inhibit this pathway, thus reducing CCD-induced neuropathic pain. Our study provides the first evidence that RUNX2 contributes to neuropathic pain via the transcriptional activation of Ccl2. A better understanding of the function of RUNX2 in neuropathic pain may be helpful for developing new therapeutic strategies.