Transauricular Vagus Nerve Stimulation (taVNS) enhances CPM in healthy subjects: A randomized controlled trial

Background Evidence suggests that transauricular vagus nerve stimulation (taVNS) modulates the endogenous pain system and may be an alternative treatment for chronic pain conditions. Objective To investigate the effects of taVNS in pain processing using quantitative sensory testing (QST) as a biomarker for pain sensitivity and modulation. Methods We conducted a randomized double-blinded controlled study with 44 healthy subjects, 22 allocated to taVNS and 22 to sham taVNS. QST metrics (pain-60, temporal summation [TSPS], and conditioned pain modulation [CPM]) were the main outcomes of the study. Self-reported mood and fatigue were secondary outcomes. We performed regression analyses to evaluate the differences between pain-60 scores, TSPS, and CPM before and after intervention comparing taVNS and sham VNS groups. Moreover, Bayesian models were performed as sensitivity analysis. Results Our findings showed a statistically significant difference in the CPM score between taVNS and sham taVNS (beta coefficient = 0.80; 95% CI: 0.23–1.37; p = 0.007). The effect size (Cohen's d) of this difference was 0.97, which is considered a large effect size. Bayesian results (non-informative prior) supported the superiority of taVNS showing a strong probability of benefit (99.99%; beta coefficient = 0.80; 95% CrI: 0.25–1.35; BF = 234.29). No differences were found in pain-60 (unadjusted: p = 0.58; adjusted: p = 0.76) or TSPS (unadjusted: p = 0.25; adjusted: p = 0.40). Moreover, the analysis demonstrated a significant correlation between VAS fatigue and mood with CPM improvement in the taVNS group. Also, changes in fatigue significantly mediated taVNS effects. Conclusions This study supports the taVNS positive effects on endogenous pain modulation in health subjects. Future RCTs using VNS in patients with chronic pain are still needed to establish the analgesic effects of taVNS in the clinical setting. Trial registration NCT05801809.