Efficacy and safety of ozone autohemotherapy for zoster-associated pain: a meta-analysis and trial sequential analysis.

OBJECTIVE

To systematically evaluate the efficacy and safety of ozone autohemotherapy (O₃-AHT) in the treatment of zoster-associated pain (ZAP).

METHODS

PubMed, Cochrane Library, Web of Science, Embase, Chinese Biomedical Database, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database were searched on September 10, 2025. We searched for randomized controlled trials evaluating O₃-AHT for ZAP management from database inception to September 10, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias. Data analysis was performed using RevMan 5.4 and Stata 18.0 software to calculate the standardized mean difference (SMD), mean difference (MD), relative risk (RR), and their 95% confidence intervals (CI). Trial sequential analysis (TSA) was conducted using TSA 0.9.5.10 software to assess the robustness of the evidence, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the quality of evidence.

RESULTS

A total of 20 studies involving 1,519 patients were included. Meta-analysis revealed that compared with the control group, O3-AHT significantly patient self-reported pain scores (visual analog scale [VAS] or numerical rating scale [NRS]) compared to controls (SMD = -1.77, 95% CI: -2.16 to -1.37, p < 0.01), improved the effective rate of pain relief (RR = 1.21, 95% CI: 1.09 to 1.33, p < 0.01), decreased inflammatory factor levels (e.g., IL-6: SMD = -1.84, 95% CI: -2.60 to -1.07, p < 0.01), and improved quality of life scores (MD = 0.75, 95% CI: 0.45 to 1.04, p < 0.01). No significant difference was observed in the incidence of adverse reactions between the two groups (RR = 0.77, 95% CI: 0.46 to 1.28, p = 0.31). However, substantial heterogeneity existed among studies (I2 often > 50%). TSA suggested that the current cumulative sample size exceeded the required information size for primary outcome (pain score), thereby supporting the reliability of the conclusion. GRADE evidence quality rating was very low to moderate, mainly limited by the risk of bias and heterogeneity of included studies.

CONCLUSION

O₃-AHT may effectively alleviate ZAP and improve the quality of life and sleep quality through anti-inflammatory and immunomodulatory mechanisms, with a favorable safety profile; moreover, combination therapy may offer greater clinical benefit. However, owing to limitations in the number and quality of included studies, further larger-scale, high-quality randomized controlled trials are warranted.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD420251145896.