Abstract Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7– 10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximate 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex through enhancing the voltage-gated K + (Kv) conductance. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising application in other nervous system diseases.
