Dong Wang, Qi Gai, Yanfeng Zhang, Zhe Yan, Bingwei Hu, Zhiying Feng
INTRODUCTION: Zoster-related neuralgia (ZRN) remains challenging to treat with current analgesics and interventional therapies. Esketamine, an N-methyl-D-aspartate receptor antagonist, offers potent analgesic effects. This study evaluated the efficacy and safety of low-dose esketamine combined with pulsed radiofrequency (PRF) for ZRN. METHODS: In this randomized controlled trial, 60 patients with ZRN scheduled for PRF were assigned to receive either continuous esketamine (0.02 mg/kg/h for 48 h) or saline alongside standard PRF and anticonvulsants. Pain (NRS, ID-pain), anxiety (HAMA), depression (HAMD-24), sleep quality (PSQI), and dissociative symptoms (CADSS) were assessed at baseline (T0), 48 h post-treatment (T1), 48 h post-treatment (T1), 1 week (T2), 2 weeks (T3), 1 month (T4), and 3 months (T5) post-treatment. Vital signs, CADSS scores (measuring dissociative symptoms), and other relevant clinical data were recorded at pre-medication (t0), 1 h (t1), 12 h (t2), 24 h (t3), and 48 h (t4) post-medication. RESULTS: Sixty patients completed the study. The esketamine group showed significantly lower NRS and ID-pain scores at all post-treatment time points (P < 0.01). HAMD-24 and PSQI scores were significantly improved from 48 h through 12 weeks (P < 0.05), while HAMA scores improved significantly from 1 week onward (P < 0.05). No significant differences in CADSS scores or adverse events were observed between groups. CONCLUSION: Low-dose esketamine combined with PRF provides effective pain relief and improves mood and sleep quality in ZRN patients with a favorable safety profile. TRIAL REGISTRATION: ChiCTR2400093061.