Transauricular Vagal Nerve Stimulation, Pressure Pain and Interoception

NCT06240026 | Completed

• 1 other identifier: N-20230022
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain, Acute

Keywords

transauricular Vagal Nerve Stimulation; Interoception; Deep Muscular Pressure Pain; Mechanism; Cardioception; Thermoception

Outcome Measures

Primary Outcomes (5)

• Pain Perception Threshold

  Pressure algometer cuffs, placed on the calf of participants, attached to an electronic visual analogue scale (VAS) measuring device will be employed. Per cuff, as it inflates, participants are asked to move the dial of the VAS when the pressure begins to be painful. The pressure at which this occurs is referred to as the pain perception threshold (PPT).

  This measurement will be taken pre-intervention, and directly post- and 30min post-intervention. It will also be taken in 5min intervals post-intervention until the PPT is back within 20% of the pre-intervention value.

• Pain Tolerance Threshold

  Pressure algometer cuffs, placed on the calf of participants, attached to a visual analogue scale (VAS) will be employed. Per cuff, as it inflates, participants are asked to move the dial of the VAS when the pressure begins to be painful. They are then tasked to accordingly move the dial as the pain increases. Importantly, when the pain becomes intolerable, participants are tasked to press the red button which releases all pressure. The pressure at which this occurs is referred to as the pain tolerance threshold (PTT).

  This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.

• Temporary Summation of Pain

  The pressure algometer cuff will inflate on the dominant leg for 1second, with a 1second break, to the given PTT 10 times consecutively. Participants are asked to move the VAS dial to the pain level at each inflation, without returning to 0 on the scale. Nothing will be done with the cuff on the opposite leg.

  This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.

• Heartbeat Perception

  Randomly interleaved and without manual help, subjects will be tasked to count their own heartbeat across 3 time-intervals (25, 35 and 45 seconds). The difference between the perceived and actual heartbeat count is defined herein as the heartbeat perception.

  This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.

• Thermal Perception

  The QST.lab thermal stimulator contains 6 stimulation regions, which can individually be programmed. First, with all regions programmed identically, participants will be tasked to state when the stimulus is perceived as painfully cold and warm. These will respectively be the cold and warm thresholds. A thermal-grid illusion pattern will then be generated: this involves interleaving stimulation regions as cold (2deg above the cold threshold) and hot (2deg below the hot threshold). Participants will then be asked to rate the pain intensity of this stimulation (0=no pain, 10=worst pain imaginable).

  This measurement will be acquired pre-intervention, and directly post- and 30min post-intervention.

Secondary Outcomes (2)

• Conditioned Pain Modulation

  This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.

• Handheld Pain Perception Threshold

  This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.

Other Outcomes (3)

• Pupil Light Reflex

  This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.

• Resting State Electroencephalography

  This measurement will be taken pre-intervention, during the intervention and post- and 30min post-intervention.

• Resting State Electrocardiography

  This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.

Study Arms (3)

transauricular Vagal Nerve Stimulation

EXPERIMENTAL

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.

Device: taVNS

Earlobe Stimulation

ACTIVE COMPARATOR

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.

Device: Earlobe Stimulation

Sham

SHAM COMPARATOR

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

Device: taVNS; Device: Earlobe Stimulation

Interventions

taVNS DEVICE

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

Sham; transauricular Vagal Nerve Stimulation

Earlobe Stimulation DEVICE

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

Earlobe Stimulation; Sham

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aalborg University: lead

Study Sites (1)

Center for Neuroplasticity and Pain

Gistrup, North Denmark, 9260, Denmark

Location

MeSH Terms

Conditions

Acute Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Electrodes for taVNS and earlobe stimulation will be placed onto the participant during both stimulation sessions. These electrodes have identical wires which are connected to a digitimer for the control of the stimulation. Researchers doing the stimulation will have no other role in the study and will not participate in patient assessment. Participants will be blinded to which stimulation type is termed 'taVNS'. And only individuals having no prior experience with taVNS will be recruited. Care will be taken not to set research appointments with participants close one to the others to avoid waiting room conversations between participants. Efficacy of blinding will be assessed at the end of the study.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: In the first experiment, participants will part-take in two identical stimulation sessions, differing only by the use of active taVNS in one session and an active control of left earlobe stimulation in the other. The sequence of sessions will be counter-balanced and randomized between participants. In the second experiment, participants will part-take in two sessions, occurring on 2 different days separated by 48h minimum. In each session, participants will undergo three 40 min stimulation, separated by 30min and differing in location, intensity and paradigm. Specifically, in one session, participants will undergo taVNS-burst-high-intensity, taVNS-continuous-high-intensity and taVNS-continuous-low-intensity (randomized). In the second session, participants will undergo earlobe-burst-high-intensity, earlobe-continuous-high-intensity and sham (in the complementary order to the other session). The sequence of sessions will be counter-balanced and randomized between participants.

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: February 2, 2024
• Study Start: March 1, 2024
• Primary Completion: August 7, 2025
• Study Completion: August 7, 2025
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)