ObjectiveThis investigation aims to evaluate the effectiveness of the paravertebral injection of recombinant human interferon-α2b in conjunction with high-voltage, long-term pulsed radiofrequency (PRF) in DRG in the mitigation of postherpetic neuralgia (PHN). MethodsThis retrospective study was performed on 84 individuals suffering from acute PHN. The participants were divided into three groups. Group H: Treat with interferon-α2b combined with high-voltage long-term PRF; Group C: Treat with high-voltage long-term PRF; Group I: Treat with the interferon-α2b. All patients in the three groups were orally administered 5 mg of morphine hydrochloride quick-release tablets when there was a burst of pain during the treatment. The pain numerical rating score (NRS), IL-6, Gal-3, and the incidence of PHN were documented prior to and following therapy. ResultsThe pain intensity of all individuals decreased following therapy. In comparison with group C, the group H NRS scores significantly reduced at 4, 8, and 12 weeks following therapy, and the PHN incidence was significantly lesser. In comparison with that prior treatment, the recommended dosage of gabapentin capsules and morphine hydrochloride tablets with an immediate release was reduced in group H. In comparison with group C, the gabapentin orally administrated capsule and morphine hydrochloride in group H reduced significantly after treatment. There were no serious adverse reactions in the three groups. ConclusionWithin the context of treatment of acute PHN, the injection of interferon-α2b in conjunction with high-voltage, long-term application of PRF is more effective than the PRF or injection of interferon-α2b alone.