Electroacupuncture combined with subanesthetic alfaxalone as a novel target for alleviating neuropathic pain

Abstract Introduction: Neuropathic pain severely affects patients' quality of life. Limited treatments offer relief but often involve long-term use and side effects. Objectives: This study aimed to explore the electroacupuncture (EA) and subanesthetic alfaxalone (ALF) combination as a novel therapeutic substitute for the treatment of neuropathic pain in a spared nerve injury (SNI) mouse model. Methods: Sixty healthy C57BL/6 male mice were randomized into 5 equal-sized groups: sham (n = 12) group, spared nerve injury (SNI; n = 12) group, SNI-ALF (n = 12), SNI-EA (n = 12), and SNI-EA-ALF (n = 12). The SNI mice received the treatment regimens at 8 days postoperatively once every 2 days for 7 treatments in total. The mechanical and thermal pain thresholds were tested after each treatment. Spinal cord samples were collected after the fourth and seventh treatments for detection of diazepam-binding inhibitor (DBI) and γ-aminobutyrate A1 isoform receptor (GABAA1). Results: Mice in the SNI-EA-ALF group showed a significant increase in mechanical and thermal pain thresholds as compared to those in the SNI-ALF and SNI-EA groups during the treatment period ( P < 0.05). A significant increase in GABAA1 expression was observed after the fourth and seventh treatments in the SNI-EA-ALF group compared to the SNI-ALF and SNI-EA groups ( P < 0.05). In addition, the DBI expression level was significantly lower in the SNI-ALF-EA group than the SNI, SNI-ALF, and SNI-EA groups ( P < 0.05). Conclusion: Our results support the use of EA, combined with ALF, to synergistically relieve pain in preclinical models of NP.