Clinical trial NCT06240026: Transauricular Vagal Nerve Stimulation, Pressure Pain and Interoception
Official title: Effects of Transauricular Vagal Nerve Stimulation on Interoceptive Channels in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain, Acute
Keywords: transauricular Vagal Nerve Stimulation
Interoception
Deep Muscular Pressure Pain
Mechanism
Cardioception
Thermoception
Lead sponsor: Aalborg University
Sponsor class: OTHER
First posted: 2024-02-02
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: OTHER

Brief 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, 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.

Detailed 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 (taVNS) 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, 30 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, 25Hz, 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, 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.

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.

Primary outcomes:
measure: Pain Perception Threshold
timeFrame: 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.
measure: Pain Tolerance Threshold
timeFrame: This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.
measure: Temporary Summation of Pain
timeFrame: This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.
measure: Heartbeat Perception
timeFrame: This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.
measure: Thermal Perception
timeFrame: This measurement will be acquired pre-intervention, and directly post- and 30min post-intervention.
Secondary outcomes:
measure: Conditioned Pain Modulation
timeFrame: This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.
measure: Handheld Pain Perception Threshold
timeFrame: This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.
Other outcomes:
measure: Pupil Light Reflex
timeFrame: This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.
measure: Resting State Electroencephalography
timeFrame: This measurement will be taken pre-intervention, during the intervention and post- and 30min post-intervention.
measure: Resting State Electrocardiography
timeFrame: This measurement will be taken pre-intervention, and directly post- and 30min post-intervention.
Locations:
city: Gistrup
country: Denmark
facility: Center for Neuroplasticity and Pain
state: Region Nordjylland
Study officials:
References: