Transauricular Vagal Nerve Stimulation, Pressure Pain and Interoception

NCT ID: NCT06240026

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2025-08-07

Brief Summary

Interoception, the ability to perceive, process and respond to signals originating from within the body, is crucial for maintaining healthy physiological ranges. Indeed, dysfunction in this ability has been associated with various mood and pain disorders. Based on the overlap between the anatomical pathway of this ability and the site of action of the tool, transauricular vagal nerve stimulation (taVNS) could modulate this interoception. However, little is known about the breadth, duration, and mechanism of interoception modulation by taVNS.

The study (Ethics Region Nord Jylland Denmark, N-20230022) will address these limitations, with 2 experiments with a focus on three interoceptive channels: deep muscular pressure pain, heartbeat, and thermal perception.

Detailed Description

The first experiment will aim to corroborate and extend the pain-modulating effect of taVNS to other interoceptive functions and to vagal-activation markers. For this, 30 healthy subjects will complete a randomized, active control, crossover study. The main intervention is left concha taVNS (NEMOS, CerboMed GmbH, Erlangen, Germany) for 20 minutes (200µs duration, 25Hz, at a personalized intensity). This will be compared to an active control of identical electrical stimulation to the left earlobe. A blinding assessment inquiring which stimulation is supposed to be therapeutic will be collected. Main outcomes are pressure pain thresholds and temporal summation of pain responses acquired via cuff-pressure algometer (Cortex Technology, Aalborg University, Denmark) placed at the calf. Heartbeat perception, assessed via the heartbeat counting task, and thermal perception, assessed using a QST thermal grid, are also primary outcomes. Secondary outcomes are conditioned pain modulation, resting state electroencephalography, electrocardiography, and pupillary light reflexes. To assess whether, and how, taVNS modulates deep muscular pressure pain, heartbeat, and thermal perception, primary and secondary measurements pre, post and 30min post stimulation will be collected and compared. To assess the duration of the potential effects, these outcomes will be collected, and compared, at 5min intervals until the primary measurements are within 20% of baseline values. Given baseline is recovered, the second stimulation session will take place. Given this has not occurred within 1.5h of the cessation of the stimulation in the first stimulation session, subjects will be asked to come back at their earliest convenience.

The second experiment will additionally explore the effect of stimulation paradigm and intensity. For this, 20 healthy subjects will complete a randomized, active and sham control, crossover study. The main intervention is left concha taVNS (NEMOS, CerboMed GmbH, Erlangen, Germany) for 40 minutes (200µs duration, 25Hz). This will be compared to an active control of identical electrical stimulation to the left earlobe and sham stimulation. Stimulation intensity will be given at 2/3rd of perception to pain threshold and at pain thresholds. A burst and continuous paradigm will also be employed. A blinding assessment inquiring which stimulation is supposed to be therapeutic will be collected. Main outcomes are pressure pain thresholds acquired via cuff-pressure algometer (Cortex Technology, Aalborg University, Denmark) placed at the calf. Heartbeat perception, assessed via the heartbeat counting task is also primary outcomes. Secondary outcomes are conditioned pain modulation, resting state electroencephalography, electrocardiography, and pupillary light reflexes. Assessments will be acquire pre, during and post stimulation.

Conditions

Pain, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

transauricular Vagal Nerve Stimulation

NEMOS taVNS electrodes will be placed in the left concha cymba of participants (CerboMed GmbH, Erlangen, Germany). When appropriate, these electrodes will be plugged into a digitimer. Whilst pulse width, frequency, stimulation burst and total duration will be respectively standardized to 200microseconds and 25Hz.

In the first experiment, continuous and 20min stimulation will be applied at one person-specific intensity. To acquire this, using an elegant stair-case algorithm, perception and supra-pain (described as a 7/10 pain level, where 10 is the most amount of pain imaginable) thresholds will be obtained. Stimulation intensity will then be defined as 2/3 the range between these thresholds.

In the second experiment, burst and continuous stimulation will be applied for 40min. Two intensities will be used: 2/3 the range between perception and supra-pain thresholds and supra-pain thresholds.

Group Type: EXPERIMENTAL

taVNS

Intervention Type: DEVICE

transauricular vagal nerve stimulation electrodes (NEMOS, CerboMed GmbH, Erlangen, Germany), attached to a digitimer.

Earlobe Stimulation

Electrodes (Ambu, Neuroline, Bordeaux, France) will respectively be placed on the front and back of the earlobe. When appropriate, these electrodes will be plugged into a digitimer . Whilst pulse width, frequency, stimulation burst and total duration will be respectively standardized to 200microseconds, 25Hz, continuous and 20minutes, the stimulation will be person specific. To acquire this intensity, participants will perform a thresholding protocol. Based on an elegant stair-case algorithm, the perception and pain (described as a 7/10 pain level, where 10 is the most amount of pain imaginable) thresholds will be obtained. Stimulation intensity will then be defined as 2/3 the range between these thresholds. For example, if the perception and pain thresholds are respectively at 2mA and 8mA, the stimulation intensity would be 6mA.

Group Type: ACTIVE_COMPARATOR

Earlobe Stimulation

Intervention Type: DEVICE

Standard electrodes (Ambu, Neuroline, Bordeaux, France) cut into 0.6cm circles, attached to a digitimer.

Sham

No current will be applied to the ear of the participant.

Group Type: SHAM_COMPARATOR

taVNS

Intervention Type: DEVICE

transauricular vagal nerve stimulation electrodes (NEMOS, CerboMed GmbH, Erlangen, Germany), attached to a digitimer.

Earlobe Stimulation

Intervention Type: DEVICE

Standard electrodes (Ambu, Neuroline, Bordeaux, France) cut into 0.6cm circles, attached to a digitimer.

Interventions

taVNS

transauricular vagal nerve stimulation electrodes (NEMOS, CerboMed GmbH, Erlangen, Germany), attached to a digitimer.

Intervention Type: DEVICE

Earlobe Stimulation

Standard electrodes (Ambu, Neuroline, Bordeaux, France) cut into 0.6cm circles, attached to a digitimer.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Are aged 18-60
• Are healthy
• Speak and understand English

Exclusion Criteria

• Are pregnant and/or breastfeeding
• Regularly use cannabis, opioids, or other drugs
• Currently or previously suffered of a neurologic, musculoskeletal, mental, or other illnesses (e.g., brain or spinal cord injuries, degenerative neurological disorders, major depression, cardiovascular disease, chronic lung disease, etc.)
• Once or more a week take of analgesic medication or other medication which may affect the trial (including paracetamol and NSAIDs)
• Have a recent history of acute pain, particularly in the lower limbs.
• Have abnormally disrupted sleep in 24 hours preceding experiment.
• Have contraindications to electric application (history of epilepsy, metal implants in head or jaw, etc.)
• Lack the ability to cooperate.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aalborg University

OTHER

Sponsor Role: lead

Responsible Party

Laura De Herde

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Center for Neuroplasticity and Pain

Gistrup, North Denmark, Denmark

Countries

Denmark

Other Identifiers

N-20230022

Identifier Type: -

Identifier Source: org_study_id