Transauricular Vagal Nerve Stimulation and Interoception

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.

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.

Eligibility Criteria:
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.