The Effect of Transcutaneous Trigeminal Nerve Stimulation and Transcutaneous Auricular Vagal Nerve Stimulation on the Biomarker Response to Stress.

Background: Transcutaneous trigeminal nerve stimulation (tTNS) and transcutaneous auricular vagal nerve stimulation (tVNS) are neurostimulation methods that have recently gained attention for their potential to modify the response to stress. However, current understanding of the effects of tVNS and tTNS on autonomic nervous system (ANS) activity in healthy individuals is limited. Therefore, this study compared the effect of tTNS and tVNS on the biochemical markers of ANS activity after an acute stress test in a cohort of young healthy adults.

Materials and methods: Participants aged 18 to 45 years were randomized to tTNS, tVNS, or sham stimulation conditions. Participants received 20 minutes of neurostimulation/sham and then completed the Trier Social Stress Test (TSST). Cortisol, sulfated dehydroepiandrosterone (DHEA-s), insulin-like growth factor-1 (IGF-I), prolactin, norepinephrine (NE), γ-aminobutyric acid (GABA), and brain-derived neurotrophic factor were measured prestimulation and then again 0, 15, 30, and 60 minutes after TSST.

Results: The TSST induced a stress response by increasing levels of cortisol, DHEA-s, prolactin, IGF-I, and NE relative to baseline. Neither tTNS nor tVNS caused significant changes in stress biomarker concentrations compared with sham, except for norepinephrine (NE). NE levels were significantly higher in participants receiving tTNS than in those receiving tVNS at both 15 minutes (p < 0.01) and 30 minutes (p < 0.02) after the TSST. In addition, NE was elevated in the tTNS group compared with sham at 15 minutes after stress (p < 0.01).

Conclusion: In this study, although tVNS and tTNS did not appear to influence biochemical markers of stress generally, tTNS was uniquely associated with elevations in NE. These findings provide evidence that tTNS may influence arousal under conditions of stress.