Acute Pain, Healthy Adult Participants, Pain Perception
Conditions
Brief summary
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.
Interventions
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.
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.
OTHERCold 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.
Sponsors
David A. Purger
Indiana University Health
Indiana University Health Methodist Hospital
Purdue University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Each participant completes three cold pressor tests in a single session. The first is always performed with no stimulation and serves as a within-subject control. Participants are then randomized to receive either active or sham stimulation first, followed by the alternate condition. Randomization uses a computer-generated allocation sequence producing two equal groups. Participants are blinded to which condition is active. Study personnel are not blinded, because condition assignment determines device placement.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain intensity measured by the Numerical Pain Rating Scale | Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes. | 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. |
| Pain intensity measured by the Visual Analogue Scale | Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes. | 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. |
| Pain threshold during cold pressor test | During each of the three cold pressor tests within a single visit, approximately 90 minutes. | Time in seconds from hand immersion to the participant's first verbalized sensation of pain, recorded separately for each hand. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in EEG spectral power | Continuously throughout a single visit, approximately 90 minutes. | 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. |
| Change in EEG functional connectivity | Continuously throughout a single visit, approximately 90 minutes. | 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. |
Countries
United States
Contacts
CONTACTCaliel Hines
CONTACTMarissa Lowe
PRINCIPAL_INVESTIGATORDavid A Purger, MD, PhD
Indiana University
Outcome results
None listed