Upregulation of Acid-Sensing Ion Channel 1a in the Anterior Cingulate Cortex by TNF-α/NF-κB Pathway Contributes to Diabetes-Related Pain

Upregulation of acid-sensing ion channel 1a (ASIC1a) expression in anterior cingulate cortex (ACC) glutamatergic (ACCGlu) neurons drives diabetes-related pain hypersensitivity in mice, and pharmacologic inhibition and genetic knockout of ASIC1a in ACCGlu neurons significantly reduce neuronal hyperactivity and alleviate pain. Tumor necrosis factor-α/nuclear factor-κB signaling in the ACC elevates ASIC1a expression, mechanistically linking neuroinflammation to pain development in diabetic mice. ASIC1a is a potential therapeutic target for diabetes-related pain, offering a pathway-specific strategy for treatment development.