Neuroplasticity:Melatonin and Transcranial Current Stimulation in Healthy Subjects.

Study Overview
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Brief Summary
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Pain exerts a tremendous cost in healthy care, rehabilitation and lost productivity. It is is associated with a wide range of diseases and their social consequences is a public health problem. With the progress of neuroscience and studies on the plasticity of the central nervous system, it has been provided a better understanding of the neurobiological mechanisms of pain. The neurohormone Melatonin stands by having systemic and diverse mechanisms of action, both in physiological and pathological situations, with modulating effects on the process of nociceptive signaling and neurochemical mechanisms such as serotonergic, opioidergic and GABAergic, exerting anti-inflammatory action, analgesic activity among others. The advent of neuromodulation techniques such as transcranial direct current stimulation (tDCS), which promote changes in neuronal activity and signaling to be effective in conditions of chronic pain by attenuating changes in cortical excitability. There is clinical evidence of the analgesic effect of Melatonin and tDCS alone. Thus, considering the potential for each isolated intervention and the lack of knowledge of their combined effect, the authors propose the present study to investigate the effect of this combination on the heat-pain detection threshold and the neuroplasticity in the healthy subjects.

Detailed Description
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The methods are according to the CONSORT guidelines. Heat pain threshold and tolerance : Quantitative Sensory Testing (QST) will be used on a computer Peltier-based device thermode. Conditioned Pain Modulation (CPM)-task: Immerssing the non-dominant hand cold water for 1 minute. Serum Brain Derived Neurotrophic Factor (BDNF). Transcranial Magnetic Stimulation (TMS) assessment: motor threshold, motor evoked potential, Short intracortical inhibition and intracortical facilitation. Statistical analyses: Descriptive statistics, Linear and multiple regression analysis, performed with SPSS version18.0.

Official Title
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Effect of Melatonin and Transcranial Direct Current Stimulation (tDCS) on Neuroplasticity and the Heat-pain Detection Threshold in Healthy Subjects:Randomized, Double-blind,Crossover Trial

Conditions
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Analgesia Disorder, Pain

Intervention / Treatment
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* Device: Transcranial Direct Current Stimulation (tDCS)
* Drug: Melatonin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male 18-40 years old Healthy Without medication Sign the informed consent Exclusion Criteria: Patients who did not understand the Portuguese Acute or chronic pain conditions Medical or psychiatric disorders History of alcohol or substance abuse Neurological disorder Use of medications affect in the central nervous system Traumatic brain injury Neurosurgery Metallic implant in the brain

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Melatonin<br>0,25mg/Kg sl before tDCS | Drug: Melatonin<br> <br> |
| Experimental: tDCS<br>Transcranial direct current stimulation once time. Dose 2 mA, 20 seconds. | Device: Transcranial Direct Current Stimulation (tDCS)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in heat-pain threshold with pain score | Heat-threshold by Pettier-based device on the contralateral hand assessment pain score (VAS) | Baseline, one week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Brain-Derived neurotrophic factor (BDNF) |  | Baseline, one week | 
| Change from Baseline from Catastrophizing Scale |  | Baseline, one week | 
| Change from baseline Inventory of state-trait anxiety Scale |  | Baseline, one week | 
| Change from baseline Inventory of Coping |  | Baseline, one week | 
| Change from baseline of cortical excitability | Transcranial Magnetic Stimulation (TMS) assessment motor threshold, motor-evoked potentials, silent period, intracortical inhibition and facilitation | Baseline, one week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melatonin, Transcranial Direct Current Stimulation, Neuroplasticity, Analgesia, Pain