Transauricular Vagal Nerve Stimulation, Pressure Pain and Interoception

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.

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.