Effects of Transcutaneous Vagus Nerve Stimulation on Pain and Brain Activity in Healthy Adults

The Effects of Transcutaneous Vagus Nerve Stimulation (tVNS) on Acute Pain Perception and Brain Activity in Healthy Adults

The goal of this clinical trial is to learn whether stimulating a nerve in the neck changes how much pain people feel. It also looks at whether this stimulation changes brain activity. The study is being done in healthy adults ages 18 to 70.

The nerve being studied is called the vagus nerve. It runs through the neck and connects to parts of the brain that handle pain. In this study, the nerve is stimulated from outside the body using a small device placed on the skin. There is no surgery, and nothing is implanted.

The main questions it aims to answer are: (1) Does stimulating the vagus nerve lower the pain people feel during a cold water test? (2) Does stimulating the vagus nerve change the electrical activity in the brain?

Researchers will compare pain ratings and brain activity under three conditions in the same person: no stimulation, real stimulation over the vagus nerve, and sham stimulation placed nearby on the neck. Sham stimulation feels similar but is not aimed at the nerve.

Participants will: (1) Come to one visit that lasts about 90 minutes, with no follow-up visits, (2) Wear a cap that records the brain's natural electrical signals for the whole visit, (3) Place both hands in cold water, about 39 degrees Fahrenheit, up to three times for up to 2 minutes each time, (4) Rate their pain after each cold water test, (5) Wear a stimulation device on the neck during two of the three cold water tests, (6) Not be told which of those two is the real stimulation until the visit is over.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Pain; Healthy Adult Participants; Pain Perception
• Intervention / Treatment: Device: Active transcutaneous vagus nerve stimulation; Device: Sham transcutaneous vagus nerve stimulation; Other: Cold pressor test

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caliel Hines; Phone Number: 317-963-7010; Email: calhines@iu.edu
• Study Contact Backup: Name: Marissa Lowe; Email: lowemj@iu.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health Neuroscience Center
      • Contact: Department of Neurological Surgery; Phone Number: 317-963-1300; Email: dpurger@iu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults aged 18 to 70 years
• Healthy, defined as having no history of chronic medical, neurological, or psychiatric conditions
• Not currently experiencing acute illness or chronic pain
• Not currently taking medications that influence the nervous system or pain sensitivity
• Willing and able to provide written informed consent in English

Exclusion Criteria:

• History of vagal or vasovagal symptoms
• Respiratory distress
• Cardiac arrhythmia
• Sleep apnea
• Pregnancy
• Substance abuse
• Primary psychiatric disorder
• Prior vagus nerve stimulation or any implanted medical device
• Significant acute or chronic neurologic illness that, in the judgment of the Principal Investigator, could compromise participant safety, limit the ability to complete the study, or compromise the objectives of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Stimulation First, Then Sham; Participants complete a cold pressor test with no stimulation, then a second cold pressor test during active transcutaneous vagus nerve stimulation, then a third during sham stimulation.	Device: Active transcutaneous vagus nerve stimulation; Stimulation applied over the cervical branch of the vagus nerve, anterior to the sternocleidomastoid along the carotid sheath. Pulse width 200 microseconds, frequency 30 Hz, rectangular monophasic waveform, intensity titrated between 17.8 and 39.5 volts to a mild tingling sensation below the threshold of discomfort. Stimulation is maintained for 20 minutes before the cold pressor test and continues throughout it.; Device: Sham transcutaneous vagus nerve stimulation; Identical device, parameters, and duration as the active condition, differing only in placement. The device is positioned slightly posterior on the neck, away from the cervical branch of the vagus nerve.; Other: Cold pressor test; Immersion of both hands up to the wrist in water maintained at 4 degrees Celsius with ice for up to two minutes or as long as tolerated. Performed three times per participant: once with no stimulation, once during active stimulation, and once during sham stimulation.
Experimental: Sham Stimulation First, Then Active; Participants complete a cold pressor test with no stimulation, then a second cold pressor test during sham stimulation, then a third during active transcutaneous vagus nerve stimulation.	Device: Active transcutaneous vagus nerve stimulation; Stimulation applied over the cervical branch of the vagus nerve, anterior to the sternocleidomastoid along the carotid sheath. Pulse width 200 microseconds, frequency 30 Hz, rectangular monophasic waveform, intensity titrated between 17.8 and 39.5 volts to a mild tingling sensation below the threshold of discomfort. Stimulation is maintained for 20 minutes before the cold pressor test and continues throughout it.; Device: Sham transcutaneous vagus nerve stimulation; Identical device, parameters, and duration as the active condition, differing only in placement. The device is positioned slightly posterior on the neck, away from the cervical branch of the vagus nerve.; Other: Cold pressor test; Immersion of both hands up to the wrist in water maintained at 4 degrees Celsius with ice for up to two minutes or as long as tolerated. Performed three times per participant: once with no stimulation, once during active stimulation, and once during sham stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity measured by the Numerical Pain Rating Scale	Participant-reported pain intensity on an 11-point scale from 0 to 10, where 0 is no pain and 10 is the worst pain imaginable. Higher scores indicate greater pain. Rated immediately after each cold pressor test.	Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes.
Pain intensity measured by the Visual Analogue Scale	Participant-reported pain intensity is marked on a 100 mm line anchored at 0 mm for no pain and 100 mm for the worst imaginable pain. The distance in millimeters from the left anchor is recorded as the score. Higher scores indicate greater pain. Rated immediately after each cold pressor test.	Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes.
Pain threshold during cold pressor test	Time in seconds from hand immersion to the participant's first verbalized sensation of pain, recorded separately for each hand.	During each of the three cold pressor tests within a single visit, approximately 90 minutes.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in EEG spectral power	Change in spectral power within canonical frequency bands (delta 1 to 4 Hz, theta 4 to 8 Hz, alpha 8 to 12 Hz, beta 13 to 30 Hz, gamma above 30 Hz), measured by continuous 16-channel electroencephalography, compared across resting baseline, stimulation without noxious stimulus, and stimulation during cold pressor test.	Continuously throughout a single visit, approximately 90 minutes.
Change in EEG functional connectivity	Change in functional connectivity between brain regions, derived from continuous 16-channel electroencephalography. Phase locking values are computed for each pair of EEG channels within canonical frequency bands, and connectivity metrics are derived from those values. Coherence is assessed in the frequency domain. Analyses are restricted to predefined, theory-driven regions and frequency bands. Compared across resting baseline, stimulation without noxious stimulus, and stimulation during the cold pressor test.	Continuously throughout a single visit, approximately 90 minutes.

Collaborators and Investigators

• Sponsor: David A. Purger
• Collaborators: Purdue University; Indiana University Health; Indiana University Health Methodist Hospital
• Investigators: Principal Investigator: David A Purger, MD, PhD, Indiana University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: September 14, 2026
• First Submitted That Met QC Criteria: September 14, 2026
• First Posted (Actual): September 18, 2026

Study Record Updates

• Last Update Posted (Actual): September 18, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Acute Pain
• Other Study ID Numbers: 27960; SNEU-IIR-TVNS-ADULTS (Other Identifier: Indiana University IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a small exploratory pilot study in healthy volunteers, designed to generate preliminary effect size estimates rather than definitive findings. With a target enrollment of 20 participants at a single site, the dataset is small enough that a decision about sharing individual participant data has been deferred. The current informed consent form does not specifically address sharing de-identified individual participant data with researchers outside the study team. Any future data sharing would require review of participant consent and approval by the Indiana University Institutional Review Board. The study team will revisit this decision before study completion.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No