Efficacy and Safety of Electroacupuncture for Postherpetic Neuralgia and Biomarker Evaluation: A Study Protocol for a Multicenter, Randomized Trial.

Introduction: Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition that endures for at least 3 months following the onset of herpes zoster, significantly impairing life quality of patients. Current PHN treatments demonstrate limited efficacy, and the lack of reliable severity biomarkers hinders effective clinical management. Electroacupuncture represents a promising therapeutic approach for PHN, though comprehensive evidence supporting its efficacy and safety is still needed. Furthermore, as objective indicators, the role of serum biomarkers in assessments still requires further investigation. Methods: This multicenter, sham-controlled, randomized study will recruit 180 patients with PHN. Participants will be allocated in a 1:1:1 ratio to electroacupuncture, sham acupuncture, or waiting-list groups via multicenter stratified block randomization. Participants will receive 1-month of treatment and 3-month follow-ups. The electroacupuncture group and the sham acupuncture group will each receive 12 treatments. All participants will maintain their pre-enrollment medication. Primary outcome is Numerical Rating Scale; secondary outcomes include pain episode frequency, Hamilton Anxiety Scale, Hamilton Depression Scale, The Short-Form 36 Health Survey, and changes of biomarkers (Neuropeptide Y, Substance P, Tumor Necrosis Factor-α, Interleukin-10). A linear mixed-effects model will be used to analyze data at different time points to explore the efficacy of electroacupuncture and the correlation between serum biomarkers and pain intensity. The predictive value of biomarkers for refractory postherpetic neuralgia (NRS reduction <30% from baseline post-treatment) will be assessed using ROC curves. Conclusion: The expected outcomes will clarify the efficacy and safety of electroacupuncture for PHN. The study will also analyze the correlation between serum biomarkers and pain symptoms and determine whether serum biomarkers can serve as prognostic indicators for refractory postherpetic neuralgia. Trial Registration: ClinicalTrials.gov identifier: NCT06990854. Registered on June 3, 2025. (https://clinicaltrials.gov/study/NCT06990854).