Transcranial Versus Suboccipital Direct Current Stimulation

Study Overview
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Brief Summary
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Randomized controlled trial, in parallel with cross-control design. Two groups of healthy subjects will be randomly selected to transcranial stimulation group or suboccipital stimulation group. Each group receive in a randomized order a real direct current session and a sham session. The study is based on the hypothesis that the application of direct current sitmulation applied at the suboccipital level produce higher modifications on endogenous pain modulation system than transcranial stimulation.

Detailed Description
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The development of the project will be based on the Declarations of the World Medical Association of Helsinki. Every subject will be informed about the nature of the study, willingness to participate, the proposed objectives, as well as possible adverse effects that may occur in its implementation. Every subject will be asked to give their signed consent to participate in the study. The study will be suspended at any time, if the patient wishes. Healthy volunteers will be recruited from the city of Toledo, between the ages of 18 and 40. The detection and selection of the sample will be carried out between the students of the University of Castilla-La Mancha and personnel of the Hospital Nacional de Parapléjicos who meet the inclusion criteria and give their consent voluntarily to participate in the study. The calculation of the sample size will be carried out using the G * Power software program (version 3.1), for clinical studies with two intervention groups. Conditioned pain modulation will be chosen as the primary outcome variable. Assuming an α level of 0.05 and a statistical power of 85%, with a moderate effect size for the ANOVA test (0.25). The experiment will be carried out in the clinical laboratory of the Sensory-Motor Function Research Group of the Hospital Nacional de Parapléjicos. Under attenuated sound conditions, and at a stable temperature in the range of (22 °C-26 °C). In the first session of the study, a small interview will be carried out to determine if there is any exclusion criterion. The initial measurements will consist of sociodemographic variables and psychological variables, which will then be used to categorize groups and analyze covariates. A parallel randomized controlled trial with cross-control design is proposed. Two groups of healthy subjects will be randomly selected to transcranial direct current stimulation (DCS) group or suboccipital DCS group. Each group receive in a randomized order and with a double blind design a real direct current session and a sham session. An assessment is made before and after each intervention. Subjects will remain in a sitting position, with their backs resting in a relaxed position. In all interventions a direct current stimulator (DC-stimulator, Neuroconn) will be used.

Official Title
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Effectiveness of Transcranial and Suboccipital Direct Current Stimulation on Endogenous Pain Modulation System in Healthy Volunteers.

Conditions
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Pain, Transcranial Direct Current Stimulation

Intervention / Treatment
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* Device: Direct Current Stimulation
* Device: Sham DCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 40 years. Healthy volunteers (without neurological injury and no history of pain in the last 6 months). Ability to perform all clinical test and understand the process of the study, as well as obtaining informed consent. Tolerance to the application of electrotherapy. Exclusion Criteria: Previous history of surgical intervention at the cervical level. Have been treated with an electric current similar to that applied prior to the intervention. Sensitivity altered in the area of application of the intervention. No commitment to continuity. History of neuromuscular disease. Epilepsy. Injuries, surgery or pain affecting the upper limb. Material of osteosynthesis at the cervical level. Diabetes. History of cancer. Cardiovascular disease. Presence of pacemakers or any other implanted electrical device. Take medication during the study and in the 7 days prior to the study. Consumption of narcotic substances during the study and in the 7 days prior to the study. Presence of tattoos or any other external agent introduced in the treatment and assessment area (hand). Pregnancy. Presence of severe and frequent headaches. Ulcers or scars in the skin at the location of the electrodes

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Paralled randomized controlled trial with cross-control design. Two groups of subjects will be randomly selected, a Transcranial stimulation group and a suboccipital stimulation group. Each group will perform two intervention sessions in a randomized order, a session with direct current stimulation and a sham stimulation session.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transcranial Stimulation<br>Transcranial stimulation on the primary motor cortex (M1) with anode located on the point C3 (10/20 EEG system), and the cathode on contralateral supraorbital zone. | Device: Direct Current Stimulation<br>* 20 minutes of direct current stimulation using an intensity of 1.5mA and electrode size of 6x4cm<br>Device: Sham DCS<br>* 20 minutes of sham stimulation. Subjects will be stimulated during the first 30 seconds. After that, a ramp down of 10 seconds and then the stimulator is turned-off.<br>|
| Active Comparator: Suboccipital Stimulation<br>Suboccipital stimulation with anode located at the upper cervical level and cathode was placed on the lateral part of right shoulder. | Device: Direct Current Stimulation<br>* 20 minutes of direct current stimulation using an intensity of 1.5mA and electrode size of 6x4cm<br>Device: Sham DCS<br>* 20 minutes of sham stimulation. Subjects will be stimulated during the first 30 seconds. After that, a ramp down of 10 seconds and then the stimulator is turned-off.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conditioned Pain Modulation | For this protocol the test stimulus (TS) and the conditioning stimulus (CS) will be applied sequentially (first CS, followed by TS), heterotopic, and contralateral. The CS temperature will be 12 °C on the cold pressor test to induce a perception of pain. The subjects will have to submerge the non-dominant hand in the cold water bath for 30s, and evaluate the CS-induced pain intensity at 10, 20, and 30s (t1, t2 and t3 respectively). After assessing CS-induced pain intensity at the 30s of immersion participants will withdraw their hand from the water bath, and will have to fix their attention to the dominant hand where TS was immediately applied. The TS-induced pain assessment at 10, 20, and 30s (t1, t2 and t3). | Baseline at 0 min | 
| Change from baseline Conditioned Pain Modulation | For this protocol the test stimulus (TS) and the conditioning stimulus (CS) will be applied sequentially (first CS, followed by TS), heterotopic, and contralateral. The CS temperature will be 12 °C on the cold pressor test to induce a perception of pain. The subjects will have to submerge the non-dominant hand in the cold water bath for 30s, and evaluate the CS-induced pain intensity at 10, 20, and 30s (t1, t2 and t3 respectively). After assessing CS-induced pain intensity at the 30s of immersion participants will withdraw their hand from the water bath, and will have to fix their attention to the dominant hand where TS was immediately applied. The TS-induced pain assessment at 10, 20, and 30s (t1, t2 and t3). | At 30 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Temporal Summation | For the evaluation of the habituation and temporal summation of pain, heat stimuli of a p-3 intensity without conditioning stimulus (CS) will be applied. The tonic heat stimulus will be applied on the surface of the tenar eminence of the dominant hand by 8 consecutive stimuli separated from each other by 1.5 seconds, evaluating the pain perceived during the first and the eighth stimulus, and at 15 seconds after the stimulation. The temperature will be determined individually, in order to reflect the general level of discomfort that the stimulus could produce according to the visual analog scale (0-10). | At 5 min | 
| Change from baseline Temporal Summation | For the evaluation of the habituation and temporal summation of pain, heat stimuli of a p-3 intensity without conditioning stimulus (CS) will be applied. The tonic heat stimulus will be applied on the surface of the tenar eminence of the dominant hand by 8 consecutive stimuli separated from each other by 1.5 seconds, evaluating the pain perceived during the first and the eighth stimulus, and at 15 seconds after the stimulation. The temperature will be determined individually, in order to reflect the general level of discomfort that the stimulus could produce according to the visual analog scale (0-10). | At 35 min | 
| Baseline Pressure Pain Threshold | To record the mechanical pain threshold, a point will be marked on the Tibialis Anterior muscle and on the dorsal surface of the right hand, specifically on the second metacarpal lateral border, approximately 3 cm proximal to the interdigital fold. This zone is especially sensitive to pressure. For registration, the digital algometer with 0.1 N increment scale (Wagner Instruments brand, model FDIX), with a circular applicator of 1 cm in diameter will be used. Once the applicator is placed perpendicular to the skin, the pressure will increase at a rate of approximately 5 N / s. Three measures will be taken with an interval between measures of 10 seconds, the average of the three measurements will be taken as threshold of pain to the pressure. | at 10 min | 
| Change from baseline Pressure Pain Threshold | To record the mechanical pain threshold, a point will be marked on the Tibialis Anterior muscle and on the dorsal surface of the right hand, specifically on the second metacarpal lateral border, approximately 3 cm proximal to the interdigital fold. This zone is especially sensitive to pressure. For registration, the digital algometer with 0.1 N increment scale (Wagner Instruments brand, model FDIX), with a circular applicator of 1 cm in diameter will be used. Once the applicator is placed perpendicular to the skin, the pressure will increase at a rate of approximately 5 N / s. Three measures will be taken with an interval between measures of 10 seconds, the average of the three measurements will be taken as threshold of pain to the pressure. | at 40 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Direct Current Stimulation, Conditioned Pain Modulation, Endogenous Pain Modulation, Temporal Summation, Pressure Pain Threshold, Pain