Antinociceptive Effect of Transauricular Electrical Vagal Nerve Stimulation

Study Overview
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Brief Summary
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This investigation is going to study whether electrical tVNS applied at the cymba of auricular conchae reduces central sensitization of experimentally induced pain in comparison with electrical sham stimulation applied at the earlobes and whether the hypoalgesic effects of tVNS disappear after pharmacological block of muscarinic receptors. Also, this investigation will examine whether tVNS is associated with activation in brain areas, involved in processing of thermal pain stimuli and emotional and vegetative modulation of thermal pain in subjects who will respond with antinociceptive reaction to tVNS.

Official Title
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Antinociceptive Effect of Transauricular Electrical Vagal Nerve Stimulation and Its Underlying Mechanisms

Conditions
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Pain, Acute

Intervention / Treatment
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* Device: TENS eco 2 Transauricular vagal nerve stimulation
* Device: Sham TENS eco 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy volunteers aged 18-45 years old, who have given informed consent at least two days free from consume of recreational drugs no local infection at the site of tVNS and pain stimulation Exclusion Criteria: psychiatric disorders abnormal skin conditions (infection, scars, psoriasis, eczema) at the site of tVNS contra-indications for MRI (e.g. claustrophobia, pregnancy, tattoos, metallic implants) history of coronary heart disease, cardiac arrhythmia, glaucoma, allergy to sulphates

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Two periods (real and sham tVNS) randomized crossover investigation in healthy volunteers
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tVNS<br>Stimulation will be applied using TENS device eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany) bilaterally at the cymba conchae of the auricles for 20 minutes. Current intensity (1-max. 10 mA) will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved. | Device: TENS eco 2 Transauricular vagal nerve stimulation<br>* Auricular electrical stimulation will be applied bilaterally using Transcutaneous Electrical Nerve Stimulation device TENS eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany). tVNS will be applied bilaterally using electrical square impulses delivered in blocks of 9 impulses with a frequency of 100 Hz and a pulse width of 200 μs emitted twice per second resulting in mixed frequency pattern of 100 Hz/2 Hz with the current intensity, that will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved.<br>|
| Sham Comparator: Sham<br>Same stimulation will be applied using TENS device eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany) to bilaterally to the earlobes for 20 minutes. Current intensity (1-max. 10 mA) will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved. | Device: Sham TENS eco 2<br>* Sham<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unpleasantness of pain | perceived unpleasantness of pain, which participants will rate continuously during the repetitive heat stimulation using a computerized visual analogue scale (CoVAS, Medoc Advanced Medical Systems, Ramat Yishai, Israel) ranging from 0 (= not unpleasant at all) to 100 (= intolerable pain). | Continuously 5 minutes during the experimental heat pain stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate | Heart rate (bpm) | Continuously 5 minutes during the experimental heat pain stimulation | 
| Blood pressure | Systolic and diastolic blood pressure | 4 times during 5 minutes of the experimental heat pain stimulation |