Electroacupuncture Alleviates Neuropathic Pain by Suppressing Ferroptosis in Dorsal Root Ganglion via SAT1/ALOX15 Signaling.

Neuropathic pain affects globally about 7-10% of the general population. Electroacupuncture (EA) effectively relieves neuropathic pain symptoms without causing any side effects; however, the underlying molecular mechanisms remain unclear. We established a chronic constriction injury (CCI)-induced rat model of neuropathic pain. RNA sequencing was used to screen for differentially expressed genes in the dorsal root ganglion after CCI and EA treatment. We identified gene markers of ferroptosis spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15) to be dysregulated in the CCI-induced neuropathic pain model. Furthermore, EA relieved CCI-induced pain as well as ferroptosis-related symptoms in the dorsal root ganglion, including lipid peroxidation and iron overload. Finally, SAT1 knockdown also alleviated mechanical and thermal pain hypersensitivity and reversed ferroptosis damage. In conclusion, we showed that EA inhibited ferroptosis by regulating the SAT1/ALOX15 pathway to treat neuropathic pain. Our findings provide insight into the mechanisms of EA and suggest a novel therapeutic target for neuropathic pain.