SIRT3 is required for the protective function of ketogenic diet on neural inflammation and neuropathic pain

experiments revealed KD-induced upregulation of uncoupling protein 2 (UCP2), sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) in the spinal dorsal horn. Importantly, SIRT3 deficiency abolished KD's protective effects against neuropathic pain and reduced BHB levels, potentially attributable to diminished expression of hepatic ketone body synthases and spinal ketone body-utilizing enzymes. These findings highlight SIRT3 as a promising therapeutic target for neuropathic pain within the ketogenic diet paradigm, providing a foundation for novel therapeutic strategies.