Transauricular Vagal Nerve Stimulation and Interoception

Pain, Acute Clinical Trial

Official title:

Effects of Transauricular Vagal Nerve Stimulation on Interoceptive Channels in Healthy Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06240026
• Other study ID #: N-20230022
• Status: Recruiting
• Phase: N/A
• Start date: February 2024
• Est. completion date: May 2024

Study information

• Verified date: January 2024
• Source: Aalborg University
• Contact: Laura De Herde, MSc.
• Phone: 93889540
• Email: lauramrdh[@]hst.aau.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is exploring whether, and for how long, taVNS may modulate deep muscular pressure pain thresholds, heartbeat, and thermal perception (Ethics Region Nord Jylland Denmark, N-20230022). To achieve this, 20 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, 20Hz, 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.

Description:

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 (tVNS) could modulate this interoception. However, little is known about the breadth, duration, and mechanism of interoception modulation by taVNS. The current study will address these limitations, with a focus on three interoceptive channels: deep muscular pressure pain, heartbeat, and thermal perception. Specifically, 20 healthy subjects will complete a randomized, active control, crossover study containing two stimulation sessions. The main intervention is left concha taVNS (NEMOS, CerboMed GmbH, Erlangen, Germany) for 20 minutes (200µs duration, 20Hz, at a personalized intensity). The active control will be identical electrical stimulation to the left earlobe. To assess blinding, a questionnaire inquiring which stimulation is supposed to be therapeutic will be collected at the end of the study. 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 and post stimulation will be collected and compared. To assess the duration of the potential effects, these outcomes will be collected, and compared, at 15min intervals until the primary measurements are within 30% 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years to 80 Years

Eligibility

Inclusion Criteria:

• Are aged 18-60
• Are healthy
• Are right-handed
• 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.

Related Conditions & MeSH terms

• Acute Pain
• Pain, Acute

Intervention

Device:
• taVNS
transauricular vagal nerve stimulation electrodes (NEMOS, CerboMed GmbH, Erlangen, Germany), attached to a digitimer.
• Earlobe Stimulation
Standard electrodes (Ambu, Neuroline, Bordeaux, France) cut into 0.5cm and 1cm rounds, attached to a digitimer.

Locations

Country	Name	City	State
Denmark	Center for Neuroplasticity and Pain	Gistrup	Region Nordjylland

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pupil Light Reflex	Using a pupilometer, covering the other eye, the size of one pupil will be measured during the light reflex. This will be done for both eyes.	This measurement will be taken pre-intervention, and directly post-intervention. It will also be taken in 15min intervals post-intervention until the PPT is back within 30% of the pre-intervention value.
Other	Resting State Electroencephalography	Using electroencephalography (g.tec medical engineering, Austria), namely a cap of electrodes conducted to the head using gel, resting state brain activity will be recorded	This measurement will be taken pre-intervention, and directly post-intervention. It will also be taken in 15min intervals post-intervention until the PPT is back within 30% of the pre-intervention value.
Other	Resting State Electrocardiography	Using electrocardiography, namely electrodes placed on the torso of participants, resting state cardiac activity will be recorded.	This measurement will be taken pre-intervention, and directly post-intervention. It will also be taken in 15min intervals post-intervention until the PPT is back within 30% of the pre-intervention value.
Primary	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-intervention. It will also be taken in 15min intervals post-intervention until the PPT is back within 30% of the pre-intervention value.
Primary	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-intervention. It will also be taken in 15min intervals post-intervention until the PPT is back within 30% of the pre-intervention value.
Primary	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-intervention. It will also be taken in 15min intervals post-intervention until the PPT is back within 30% of the pre-intervention value.
Primary	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-intervention.
Primary	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-intervention.
Secondary	Conditioned Pain Modulation	The non-dominant leg will receive a continuous pressure of 70% of the PTT previously registered. The cuff on the dominant leg will gradually inflate. As this occurs, participants are once again asked to start moving the dial when the pressure begins to be painful, and to press the red button when this becomes intolerable.	This measurement will be taken pre-intervention, and directly post-intervention. It will also be taken in 15min intervals post-intervention until the PPT is back within 30% of the pre-intervention value.
Secondary	Handheld Pain Perception Threshold	For each side separately, a handheld pressure algometer will be applied at a constant rate of 30kPa/s, perpendicularly to the belly of the musculus trapezius. Participants will be instructed to press a button when they first perceive the pressure to be painful. This is referred to as the handheld pain perception threshold.	This measurement will be taken pre-intervention, and directly post-intervention. It will also be taken in 15min intervals post-intervention until the PPT is back within 30% of the pre-intervention value.