5‑HT in the dorsal raphe nucleus is involved in the effects of 100‑Hz electro‑acupuncture on the pain‑depression dyad in rats

Abstract

The pain‑depression dyad is becoming widespread in the clinic and is attracting increasing attention. A previous study by our group found that 100‑Hz electro‑acupuncture (EA), but not 2‑, 50‑and 2/100‑Hz EA, was effective against the reserpine‑induced pain‑depression dyad. This finding is in contrast to the fact that low‑frequency EA is commonly used to treat supraspinal‑originating diseases. The present study aimed to investigate the mechanism underlying the effects of 100‑Hz EA on the pain‑depression dyad. Repeated reserpine injection was found to induce allodynia and depressive behav­iors in rats. It decreased 5‑hydroxytryptamine (5‑HT) levels and immunoreactive expressions in the dorsal raphe nucleus (DRN). 100‑Hz EA alleviated the pain‑depression dyad and upregulated 5‑HT in the DRN of reserpine‑injected rats. Intracerebroventricular injection of para‑chlorophenylalanine, an inhibitor of 5‑HT resynthesis, suppressed the upregulation of 5‑HT in the DRN by 100‑Hz EA and partially counteracted the analgesic and anti‑depressive effects of 100‑Hz EA. The present study was the first to demonstrate that 5‑HT in the DRN is involved in mediating the analgesic and anti‑depres­sive effects of 100‑Hz EA on the pain‑depression dyad. This finding provided a scientific basis for high‑frequency EA as a potential treatment for the pain‑depression dyad.