IntroductionThe aim of this work is to examine the efficacy and benefits of ultrasound (US)-guided thoracic paravertebral block (TPVB) using paraventricular oblique sagittal (POS) approach for the treatment of herpes zoster related acute pain (ZAP) and its preventive effects on post-herpetic neuralgia (PHN).MethodsA total of 136 patients suffering from ZAP within 2 weeks of rash onset were randomly allocated to transverse short axial approach (TSA) and paraventricular oblique sagittal (POS) group in 1:1 ratio. All patients received a standard antiviral treatment and rescue analgesics besides TPVB. Primary outcome was HZ illness burden (HZ-BOI) measured by a severity-by-duration composite pain assessment during 30 days. The non-inferiority margin (NIM) was set at - 10. Secondary outcomes included visual analog pain scores (VAS) and Kolcaba's General Comfort Questionnaire discomfortable scores (GCQ) during block needle insertion, quality of life (QoL), and PHN incidence during follow-up. Adverse events were also recorded.ResultsVAS pain scores (30 (IQR: 20, 40) vs. 65 (IQR: 45, 90), p < 0.001) and GCQ discomfortable scores (p < 0.001) were significantly lower in the POS group during needle insertion. The POS approach was not inferior to the proved TSA method in terms of BOI-30(AUC) when the lower limit of 95% confidence interval (CI) of two mean differences (13.54 (95% CI - 3.55, 30.63)) lay within the NIM. There were no differences between the two groups in BOI-30-90(AUC), and BOI-90-180(AUC) (p = 0.260 and 0.182). Greater QoL improvement and lower PHN incidence were comparable between the two groups. No serious adverse events occurred.ConclusionsUS-guided TPVB using less-invasive POS technique was as an optimal early intervention to reduce ZAP and a possible preventive strategy for PHN.