Neuropathic pain has become a global public problem and health burden. Pharmacological interventions are the primary treatment, but the drug cure rate is low with side effects. There is an urgent need to develop novel treatment approaches. High frequency electrical stimulation (KHES) has been widely applied in clinical analgesia. However, its mechanism is poorly understood. In this study, datasets related to neuropathic pain were obtained from the GEO database. The differentially expressed genes (DEGs) and key genes were analyzed through functional enrichment analysis, showing that most of the pathways involve the inflammation. The MyD88 and NFκB pathways were further studied. KHES significantly alleviated mechanical and thermal allodynia in chronic constriction injury of the sciatic nerve mice. KHES also inhibited the increase in Myd88 and p-NFκB expression. The administration of NFκB pathway activator partly reversed the antinociceptive effects of KHES, and NFκB pathway inhibitor achieved analgesic effects similar to those of KHES. Therefore, KHES might be a novel intervention for the treatment of neuropathic pain.