The Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Pain and Mood in Patients with Neuropathic Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: The treatment of neuropathic pain (NP) remains a major clinical challenge. Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging neuromodulatory therapy whose efficacy and durability require systematic evaluation. This study aimed to systematically review and meta-analyze randomized controlled trial (RCT) evidence on the short-term (1 week), medium-term (4 weeks), and long-term (12 weeks) effects of taVNS on pain relief and mood improvement in patients with NP. METHODS: PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov, the Chinese Clinical Trial Registry, and China National Knowledge Infrastructure were searched from inception to 30 November 2025 for RCTs comparing adjunctive genuine taVNS with sham taVNS in patients with NP. Two researchers independently screened studies and extracted data. Risk of bias was assessed using the Cochrane RoB 2 tool, and evidence certainty was rated using the Grading of Recommendations Assessment, Development and Evaluation. A random-effects model was pre-specified for all analyses, and each follow-up time point was analyzed as a separate outcome. RESULTS: Six RCTs (324 patients) were included. taVNS was associated with a moderate reduction in pain at 1 week (SMD -0.64, 95% CI -0.86 to -0.41, P < 0.00001; low certainty) and a large reduction at 4 weeks (SMD -0.85, 95% CI -1.28 to -0.43, P < 0.0001; low certainty), whereas the 12-week effect was negligible and non-significant (SMD -0.06, 95% CI -0.34 to 0.21; low certainty), a finding that should be considered inconclusive given the limited statistical power of three trials. Anxiety improved at 1 week (SMD -0.57, 95% CI -1.07 to -0.06; very low certainty, two trials), and the clinical response rate was higher with taVNS (RR 2.14, 95% CI 1.29 to 3.55; moderate certainty). No device-related serious adverse events were reported. CONCLUSION: Adjunctive taVNS was associated with short-term reductions in pain intensity in patients with NP, based on evidence of low certainty; the durability of the effect beyond the treatment period remains uncertain, and evidence for benefits on mood is sparse. taVNS is therefore a promising intervention that requires further validation in adequately powered, rigorously designed RCTs before its clinical implementation can be recommended.