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Objectives: Varicella-zoster virus (VZV) can induce herpes zoster (HZ) and postherpetic neuralgia (PHN). Immune cells play an important role in regulating HZ and PHN pathogenesis, but the dynamic immune profiles and molecular mechanisms remain unclear. This study aimed to screen dynamic immune signatures during HZ progression and elucidate the mechanism of VZV-specific T cells in PHN., Methods: We used cytometry by time-of-flight (CyTOF) to analyze peripheral blood mononuclear cells (PBMC) samples from 45 patients with HZ and eight age-sex-matched healthy controls, eight PHN samples and seven non-PHN samples. Correlations between the immune subsets and clinical pain-related scores were performed. Further, the characteristics of VZV-specific T cells between PHN and non-PHN patients were evaluated by VZV peptide pools stimulation. The expression level of cytokines, including granzyme B, interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was performed via cytometric bead array. Finally, we analyzed the alteration of Ca 2+ signals in dorsal root ganglion (DRG)-derived cells after TNF-α stimulation., Results: We investigated the dynamic characteristics of the immune landscape of peripheral blood samples of patients with HZ and PHN, and depicted two major dynamic signatures in NK, CD4 + and CD8 + T subsets in patients with HZ, which closely correlated with clinical pain-related scores. The frequency of PD-1 + CD4 + T cells, VZV-specific PD-1 + CD4 + T cells, and the amount of TNF-α produced by VZV-specific T cells were higher in patients with PHN than without PHN. Furthermore, we showed that TNF-α could induce calcium influx in DRG-derived cells in a dose-dependent manner., Conclusions: Our results profiled the dynamic signatures of immune cells in patients with HZ and highlighted the important role of VZV-specific T cells in the pathogenesis of PHN., Competing Interests: A patent application has been submitted based in part on results presented in this manuscript. QP, XG, XZ and ZF are listed as the inventors. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peng, Guo, Luo, Wang, Zhong, Zhu, Li, Zeng and Feng.)

Introduction: Zoster-associated pain (ZAP), which may cause anxiety, depression, and sleep disorders and reduce quality of life, is often refractory to current standard treatments. Studies have shown that pulsed radiofrequency (PRF) can alleviate ZAP and reduce the incidence of postherpetic neuralgia (PHN). This study aimed to explore the clinical characteristics associated with PRF responsiveness, develop a model for identifying risk factors of inadequate PRF management, and help clinicians make better decisions. Methods: Patients who underwent PRF for ZAP between January 2017 and October 2020 in our hospital were included in this study. Patients were evaluated using the numerical rating scale (NRS), Insomnia Severity Index, Patient Health Questionnaire-9, and 36-Item Short Form Health Survey (SF-36) before and 3 months after the procedure. Patient demographic data and blood test results were also collected. We defined the effectiveness of PRF for ZAP as relief of > 50% in NRS scores compared to pre-PRF. Least absolute shrinkage and selection operator (LASSO) regression analyses were subsequently performed to identify factors related to the therapeutic effect of PRF in patients with ZAP. The performance of the prediction model was assessed by the area under the receiver operating characteristic curve (AUC). Results: The effectiveness of PRF in patients with ZAP was 69.6% (total 313 patients) after 3 months. LASSO regression analysis extracted the seven most powerful features in the developed prediction model: sex, stage of herpes zoster (HZ), pregabalin dose, bodily pain indicators of SF-36, lymphocyte count, and low-density lipoprotein cholesterol (LDLC) and complement C4 in peripheral blood. Model = 1.586 + 0.148 × lymphocyte + (−0.001) × bodily pain indicators of SF-36 + (−0.001) × pregabalin dose + 0.028 × LDLC + 0.001 × C4 + (−0.508) × sex + (−0.128) × stage of HZ. We generated the ROC curve for the prediction model, and the final AUC was 0.701. The sensitivity, specificity, and overall accuracy of the model were 90%, 33%, and 73%, respectively. Conclusions: Seven factors were significantly associated with poor PRF outcome: male sex, advanced stage of HZ, higher pregabalin dose, higher bodily pain indicators of SF-36, and lower lymphocyte count, LDLC, and complement C4 in the peripheral blood. PRF should be applied to patients with ZAP as early as possible to achieve satisfactory outcomes. [ABSTRACT FROM AUTHOR]