Background & Aims

Evidence suggests that transauricular vagus nerve stimulation (taVNS) is able to modulate the endogenous pain system and may be an alternative treatment for chronic pain conditions. Our study aims to investigate whether taVNS can change 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 the 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 were a significant mediator of the 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.

References

[1]Chakravarthy K, Chaudhry H, Williams K, Christo PJ. Review of the Uses of Vagal Nerve Stimulation in Chronic Pain Management. Current pain and headache reports 2015;19(12):54.
[2]Ben-Menachem E, Revesz D, Simon BJ, Silberstein S. Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. European journal of neurology 2015;22(9):1260-8.
[3]Ventureyra ECG. Transcutaneous vagus nerve stimulation for partial onset seizure therapy. Child’s Nervous System 2000;16(2):101-2.
[4]Yu Y, Ling J, Yu L, Liu P, Jiang M. Closed-Loop Transcutaneous Auricular Vagal Nerve Stimulation: Current Situation and Future Possibilities. Frontiers in human neuroscience 2021;15:785620.
[5]Badran BW, Dowdle LT, Mithoefer OJ, LaBate NT, Coatsworth J, Brown JC, et al. Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. Brain stimulation 2018;11(3):492-500.
[6]Ramaswamy S, Wodehouse T. Conditioned pain modulation-A comprehensive review. Neurophysiologie clinique = Clinical neurophysiology 2021;51(3):197-208.
[7]Busch V, Zeman F, Heckel A, Menne F, Ellrich J, Eichhammer P. The effect of transcutaneous vagus nerve stimulation on pain perception–an experimental study. Brain stimulation 2013;6(2):202-9.
[8]Mayer JD, Gaschke YN. The experience and meta-experience of mood. Journal of Personality and Social Psychology 1988;55(1):102-11.
[9]Granot M, Weissman-Fogel I, Crispel Y, Pud D, Granovsky Y, Sprecher E, et al. Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: do conditioning stimulus painfulness, gender and personality variables matter? Pain 2008;136(1-2):142-9.

Presenting Author

Kevin Pacheco-Barrios

Poster Authors

Kevin Pacheco-Barrios

MD, MPH, MSc

Spaulding Rehabilitation Hospital, Harvard Medical School.

Lead Author

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Anna Carolyna Gianlorenco

Spaulding Rehabilitation Hospital, Harvard Medical School

Lead Author

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Lucas Camargo

Spaulding Rehabilitation Hospital, Harvard Medical School

Lead Author

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Maria Fernanda Andrade Andrade

Spaulding Rehabilitation Hospital, Harvard Medical School

Lead Author

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Hyuk Choi

Neurive Co., Ltd., Gimhae, Republic of Korea

Lead Author

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Jae-Jun Song

Neurive Co., Ltd., Gimhae, Republic of Korea

Lead Author

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Felipe Fregni

Spaulding Rehabilitation Hospital, Harvard Medical School

Lead Author

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Topics

  • Treatment/Management: Interventional Therapies – Neuromodulation