Transcutaneous Auricular Vagus Nerve Stimulation Attenuates Early Increases in Heart Rate Associated With the Cold Pressor Test

Abstract

Introduction: Transcutaneous auricular vagus nerve stimulation (taVNS) may be useful in treating disorders characterized by chronic parasympathetic disinhibition. Acute taVNS decreases resting heart rate in healthy individuals, but little is known regarding the effects of taVNS on the cardiac response to an acute stressor. To investigate effects on the acute stress response, we investigated how taVNS affected heart rate changes during a cold pressor test (CPT), a validated stress induction technique that reliably elicits a sympathetic stress response with marked increases in heart rate, anxiety, stress, and pain.

Materials and methods: We recruited 24 healthy adults (ten women, mean age = 29 years) to participate in this randomized, crossover, exploratory trial. Each subject completed two taVNS treatments (one active, one sham) paired with CPTs in the same session. Order of active versus sham stimulation was randomized. Heart rate, along with ratings of anxiety, stress, and pain, was collected before, during, and after each round of taVNS/sham + CPT.

Results: In both stimulation conditions, heart rate was elevated from baseline in response to the CPT. Analyses also revealed a difference between active and sham taVNS during the first 40 seconds of the CPT (Δ heart rate [HR] = 12.75 ± 7.85 in the active condition; Δ HR = 16.09 ± 11.43 in the sham condition, p = 0.044). There were no significant differences in subjective ratings between active and sham taVNS.

Conclusions: In this randomized, sham-controlled study, taVNS attenuated initial increases in HR in response to the CPT. Future studies are needed to investigate the effects of various taVNS doses and parameters on the CPT, in addition to other forms of stress induction.

Clinical trial registration: The Clinicaltrials.gov registration number for the study is NCT00113453.

Keywords: Brain stimulation; cold pressor test; stress response; taVNS; vagus nerve.

Figure 1.

Electrode placement for taVNS and recording physiological parameters. EKG electrodes were attached to the subject’s chest in the locations marked on the diagram. taVNS electrodes were attached to the subject’s left cymba conchae (anode) and tragus (cathode).

Figure 2.

Δ HR during concurrent taVNS and CPT. Change in HR from baseline during the cold pressor test. The blue rectangle represents the 2-minute duration of concurrent stimulation and CPT. Heart rate is plotted in 10-second averages over time during four blocks: Anticipation (2 minutes before CPT), S1 (first 40-second block of CPT), S2 (second 40-second block of CPT), S3 (last 40 seconds of CPT), and Decline (2 minutes after CPT). Baseline HR was measured as an average of the subject’s HR during the 2 minutes before the anticipation period. Error bars are standard error of the mean. bpm, beats per minute. *S1 had between-group significance (p < 0.05).

Figure 3.

Effect on anxiety, pain, and distress. Change in subjective ratings of anxiety, pain, and distress from baseline to concurrent stimulation/CPT. There were no significant differences between the active taVNS and sham stimulation groups regarding subjective ratings.