Electroacupuncture Regulates Sympathetic Nerve Through the NTSGlu‐RVLM Circuit to Relieve Spontaneous Pain in SNI Rats

Patients suffering from neuropathic pain often experience sympathetic dysfunction. Acupuncture has shown promise in alleviating pain and modulating the activity of the autonomic nervous system. This study aims to explore the potential mechanism through which electroacupuncture (EA) modulates sympathetic nerves to alleviate neuropathic pain. Spared nerve injury (SNI) was utilized to induce neuropathic pain. EA was administered at acupoints Huantiao and Yanglingquan for 30 min every other day after SNI. Pain behavior was evaluated using paw withdrawal thresholds (PWTs) and spontaneous pain scores. Various techniques including immunofluorescence, viral tracing, electrophysiology, and chemogenetic manipulations were employed to investigate the impact of EA on the sympathetic nerves and pain behaviors, specifically through the nucleus tractus solitarii (NTS)Glu-rostral ventrolateral medulla (RVLM) circuit. In SNI rats, EA alleviated both mechanical and spontaneous pain, diminished sympathetic nerve excitability, and inhibited sympathetic nerve sprouting within the dorsal root ganglia (DRG), reduced the excitability of glutamatergic neurons in the NTS which project to the RVLM. Chemogenetic inhibition of the NTSGlu-RVLM circuit produced the same effect as EA in spontaneous pain, sympathetic nerve excitability, extracellular discharge frequency in RVLM, but not in mechanical pain. Similarly, chemogenetic activation of the NTSGlu-RVLM circuit negated the analgesic effects of EA on spontaneous pain while not affecting mechanical pain. This study suggested that EA alleviates spontaneous pain rather than mechanical pain by regulating the sympathetic nerve activity via the NTSGlu-RVLM circuit.