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31 reviewsSUMMARYExisting treatments for chronic pain often prove ineffective and carry adverse side effects, highlighting theneed for better analgesics, including non-pharmacological treatments. We demonstrate that transcutaneous electrical nerve stimulation (TENS), when repeatedly applied during the early phase of nerve injuryin mice, produces sustained analgesic effects by activating the dorsal column nucleus (DCN)-thalamiccortical pathway, which transmits vibration, discriminative touch, and proprioception. Mechanistically,TENS selectively activates glutamatergic neurons in the DCN (DCNGlu) via exciting Aβ low-threshold mechanoreceptors (Aβ-LTMRs) in dorsal root ganglia (DRGs). These DCNGlu neurons project to a distinct subsetof glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPLDCN, Glu), separate from neuronsreceiving spinal dorsal horn input (VPLSDH, Glu). VPLDCN, Glu neurons form monosynaptic connections withlayer 5 neurons in the somatosensory hindlimb cortex (S1HL), mediating TENS-induced analgesia. Our findings disclosed a neural basis of TENS-mediated pain relief and offered a promising therapeutic target forneuropathic pain.