[Adjunctive agents for nerve blocks/local injections in the treatment of zoster-associated pain: A systematic review based on levels of evidence].

objectivesZoster-associated pain (ZAP) is an acute and chronic neuropathic pain condition caused by reactivation of varicella-zoster virus in sensory ganglia, which can severely impair patients' quality of life. Nerve block is one of the most commonly used interventional techniques in clinical practice and is often combined with various adjunctive agents to enhance therapeutic efficacy. However, these agents differ in mechanisms of action and levels of evidence, and due to differences in the pathological mechanisms at different stages of ZAP, there is currently a lack of systematic evaluation based on disease staging, resulting in insufficient precision in clinical decision-making. This study aims to systematically evaluate the clinical evidence for different adjunctive agents and clarify their application value at different stages of the disease course, thereby providing a reference for individualized treatment.

methodsRelevant literature published up to December 31, 2025, was systematically searched in PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform. Inclusion criteria were: 1) Patients diagnosed with acute herpes zoster (AHZ) or postherpetic neuralgia (PHN); 2) interventions involving drugs used as adjuncts in nerve blocks or local injections; 3) randomized controlled trials (RCT), prospective cohort studies, or case-control studies. Two reviewers independently performed literature screening and data extraction. Extracted data included first author, publication year, sample size, type of nerve blocks or local injections, type and dosage of adjunctive agents, and main outcome measures. The level of evidence was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria, and adjunctive agents were graded according to the highest level of evidence.

resultsA total of 29 clinical studies were included. Based on the level of evidence, adjunctive agents were categorized into level A and level B evidence groups. Among level A evidence agents, glucocorticoids relieve pain through potent anti-inflammatory effects, while botulinum toxin type A exerts analgesic effects by inhibiting the release of pain mediators and modulating neural signaling. Among level B evidence agents, platelet-rich plasma promotes nerve repair by releasing growth factors; medical ozone exerts effects through anti-inflammatory action and improvement of circulation; methylene blue provides long-term analgesia by ameliorating reversible demyelinating nerve injury; and vaccinia virus-inoculated rabbit inflammatory skin extract (Neurotropin) may regulate pain by activating descending inhibitory pathways. Based on disease stage, anti-inflammatory treatment (e.g., glucocorticoids) is recommended in the acute phase, whereas neuromodulation and nerve repair (e.g., botulinum toxin type A, platelet-rich plasma) are emphasized in the chronic phase. All adjunctive agents require careful consideration of their specific potential serious adverse events.

conclusionsThe use of adjunctive agents in nerve blocks/local injections provides a multi-mechanistic and stage-specific therapeutic strategy for ZAP. Glucocorticoids and botulinum toxin type A have the highest level of supporting evidence. However, challenges remain, including heterogeneity in evidence levels and lack of standardized protocols. Future high-quality, large-scale randomized controlled trials, especially those comparing different adjunctive agents across disease stages, are needed to further optimize clinical treatment strategies.