Impaired Brain Astrocytic Glycolysis in Neuropathic Pain: Insights from Transcriptomic Profiling to Metabolic...

Neuropathic pain is a chronic disorder marked by sensory hypersensitivity and affective disturbances, yet current treatments often provide limited relief. Research on astrocytes in pain has focused largely on spinal mechanisms. Whether chronic peripheral nerve injury alters brain astrocytic metabolism remains unclear. Here, we isolated astrocytes from whole-brain preparations of adult mice after spared nerve injury (SNI) for transcriptomic profiling and identified coordinated suppression of astrocytic glycolysis, characterized by downregulation of genes (Aldoc, Pfkp, Pfkm, Slc2a12, and Slc2a13). Real-time Seahorse flux analysis showed reduced glycolytic activity and glycolytic capacity in SNI-derived astrocytes. We administered sodium acetate, an energy substrate preferentially utilized by astrocytes, intracerebroventricularly. Compared with vehicle treatment, acetate increased glycolytic activity and capacity in isolated astrocytes and partially improved pain-related behaviors in SNI mice. Our findings identify reduced glycolytic function in astrocytes isolated from whole-brain preparations after SNI. These findings support further investigation of astrocytic metabolism as a potential therapeutic target for chronic pain and its affective consequences.