Electroacupuncture reduced morphine tolerance in mice by suppressing brainstem signaling changes linked to diminished pain relief.
Mice received repeated morphine treatment to induce reduced analgesic responsiveness, while electroacupuncture was applied daily at the Zusanli and Sanyinjiao acupuncture points. Pain sensitivity was assessed using tail-withdrawal and heated-surface tests, and brainstem tissue was analysed through ribonucleic acid sequencing, enzyme-linked immunosorbent assays, and protein analysis.
Repeated morphine exposure reduced its pain-relieving effectiveness, whereas electroacupuncture restored morphine sensitivity. This improvement was associated with lower brainstem cyclic adenosine monophosphate activity and reduced activation of protein kinase A, extracellular signal-regulated kinase, and cyclic adenosine monophosphate response element-binding protein, suggesting that electroacupuncture counteracts tolerance through this signaling pathway.