Non-invasive Modulation of Spinal Cord Nociceptive Reflexes

Study Overview
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Brief Summary
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The aims of this study are threefold. First, to investigate whether spinal nociceptive processing - represented here by the nociceptive flexion reflex (NFR) - is influenced by thoracic transcutaneous spinal direct current stimulation (tsDCS) in a spatially selective manner, i.e., whether effects are only observed for lower limb NFRs, but not for upper limb NFRs. Second, to investigate - in a double-blind, sham-controlled, within-participant design - whether anodal and cathodal tsDCS do affect the NFR in a polarity-dependent manner. Third, to investigate whether tsDCS effects observed on a spinal measure (NFR) are also observed in responses that are mediated supra-spinally, namely autonomic parameters and pain intensity ratings.

Official Title
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Non-invasive Investigation of Excitability Changes in the Human Spinal Cord: the Effect of Transcutaneous Spinal Direct Current Stimulation (tsDCS) on Nociceptive Flexion Reflexes

Conditions
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Pain

Intervention / Treatment
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* Other: Transcutaneous spinal direct current stimulation (tsDCS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers between the ages of 18 and 40 years Having participated in the MRI medical assessment session and consented to taking part in 3T MRI measurements in written form Having participated in the magnetic/electric neurostimulation medical assessment session and consented to taking part in magnetic/electric neurostimulation experiments in written form Voluntary participation and signing of the study-specific consent form Exclusion Criteria: Existence of any contraindications for MRI measurements and magnetic/electric neurostimulation experiments Pregnancy or breastfeeding Very dry or sensitive skin (e.g., intolerance to creams/shampoos) Chronic skin diseases - such as eczema or neurodermatitis - in the area of somatosensory / nociceptive stimulation (arm or hand, leg or foot) or electrophysiological data recording (upper body, arm, leg) Scar tissue in the area of somatosensory / nociceptive stimulation (arm or hand, leg or foot) or electrophysiological data recording (upper body, arm, leg) Acute sunburn in the area of somatosensory / nociceptive stimulation (arm or hand, leg or foot) or electrophysiological data recording (upper body, arm, leg) Current or recurring pain Injuries to the nervous system History of or current neurological or psychiatric disorders Chronic diseases that require permanent medication (e.g., asthma, diabetes mellitus, etc.) Persons not capable of giving consent (e.g., in case of dementia) Lack of consent with regards to report of incidental findings

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anodal thoracic tsDCS<br>Anodal tsDCS will be applied over the T12 vertebra | Other: Transcutaneous spinal direct current stimulation (tsDCS)<br>* tsDCS will be carried out using a direct current stimulator (DC-Stimulator Plus, neuroConn, Ilmenau, Germany), with one electrode placed above the thoracic spinal cord and the other electrode placed on the right shoulder. We will employ rectangular electrodes of 7 x 5 cm size (neuroConn, Ilmenau, Germany) covered by electrode paste (Ten20 Conductive Paste, Weaver and Company, Aurora, USA). Stimulation will consist of the following phases: a fade-in period of 15 seconds, a plateau period of 20 minutes (with stimulation at 2.5mA either anodally or cathodally) and a fade-out period of 15 seconds. Sham stimulation will follow the anodal montage with 15-second fade-in and fade-out periods, but only 45 seconds of plateau stimulation at 2.5 mA. Such a combination of stimulation and electrodes results in a current density of 0.071mA/cm2, well below thermal and histological limits for current density.<br>|
| Experimental: Cathodal thoracic tsDCS<br>Cathodal tsDCS will be applied over the T12 vertebra | Other: Transcutaneous spinal direct current stimulation (tsDCS)<br>* tsDCS will be carried out using a direct current stimulator (DC-Stimulator Plus, neuroConn, Ilmenau, Germany), with one electrode placed above the thoracic spinal cord and the other electrode placed on the right shoulder. We will employ rectangular electrodes of 7 x 5 cm size (neuroConn, Ilmenau, Germany) covered by electrode paste (Ten20 Conductive Paste, Weaver and Company, Aurora, USA). Stimulation will consist of the following phases: a fade-in period of 15 seconds, a plateau period of 20 minutes (with stimulation at 2.5mA either anodally or cathodally) and a fade-out period of 15 seconds. Sham stimulation will follow the anodal montage with 15-second fade-in and fade-out periods, but only 45 seconds of plateau stimulation at 2.5 mA. Such a combination of stimulation and electrodes results in a current density of 0.071mA/cm2, well below thermal and histological limits for current density.<br>|
| Sham Comparator: Sham thoracic tsDCS<br>Sham tsDCS will be applied over the T12 vertebra | Other: Transcutaneous spinal direct current stimulation (tsDCS)<br>* tsDCS will be carried out using a direct current stimulator (DC-Stimulator Plus, neuroConn, Ilmenau, Germany), with one electrode placed above the thoracic spinal cord and the other electrode placed on the right shoulder. We will employ rectangular electrodes of 7 x 5 cm size (neuroConn, Ilmenau, Germany) covered by electrode paste (Ten20 Conductive Paste, Weaver and Company, Aurora, USA). Stimulation will consist of the following phases: a fade-in period of 15 seconds, a plateau period of 20 minutes (with stimulation at 2.5mA either anodally or cathodally) and a fade-out period of 15 seconds. Sham stimulation will follow the anodal montage with 15-second fade-in and fade-out periods, but only 45 seconds of plateau stimulation at 2.5 mA. Such a combination of stimulation and electrodes results in a current density of 0.071mA/cm2, well below thermal and histological limits for current density.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in NFR amplitude | 90-150ms for lower limb, 60-200ms for upper limb | Baseline and immediately after the intervention | 
| Change in pain intensity rating | One rating per trial on a standard visual analogue scale (VAS); internally numbered from 0 (no sensation) to 100 (unbearable pain) | Baseline and immediately after the intervention | 
| Change in skin conductance response | Amplitude maximum before onset of pain rating | Baseline and immediately after the intervention | 
| Change in heart period acceleration | Amplitude maximum before onset of pain rating | Baseline and immediately after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in NFR area | 90-150ms for lower limb, 60-200ms for upper limb | Baseline and immediately after the intervention |