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Transcranial Direct Current Stimulation Effect on Pain Threshold and Working Memory: Impact of Age and Protocol Type

Not Applicable
Completed
Conditions
Working Memory
Pain
Transcranial Direct Current Stimulation
Interventions
Device: Sham tDCS
Device: Anodal tDCS on M1
Device: Anodal tDCS on DLPFC
Registration Number
NCT04328545
Lead Sponsor
Hospital de Clinicas de Porto Alegre
Brief Summary

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation method which has great potential as an aid in the therapeutic management of neuropsychiatric disorders and chronic pain syndromes. However, despite promising results, the response to stimulation presents great variability among subjects. Age is a factor that is known to influence the tDCS effect forging the inconsistency of clinical effect.The purpose of this study is to evaluate the effect of tDCS on pain perception and working memory in healthy women from 3 different age groups: adolescents, young adults and elderly. This is a randomized, single-blinded, cross-over study of 2 different active interventions and sham.

Detailed Description

Transcranial direct current stimulation (tDCS) is a neuromodulation method that has great potential as an aid in the therapeutic management of neuropsychiatric disorders and chronic pain syndromes. tDCS modulates the neuronal membrane potential , facilitating neuronal depolarization or hyperpolarization, hence modifying the cortical excitability of the stimulated area. However, despite promising results the response to stimulation presents great variability among subjects. Chronological age is an important factor in the variation of brain plasticity. The dorsolateral prefrontal cortex (DLPFC) is associated with cognitive and emotional aspects of pain, in addition to being related to executive components of working memory. Anodal tDCS on DLPFC modulates pain level in patients with chronic pain and modifies working memory performance in healthy subjects and patients with memory impairment. The prefrontal cortex presents a great structural difference throughout lifespan: it is under maturational process in the adolescence, reaching peak of maturation in the adult life, and initiating process of cerebral senescence in elderly subjects. Therefore, the use of tDCS on DLPFC in these three age groups presents potential for a large variation in response. Faced with the potential of tDCS for adjuvant use in the treatment of several diseases, it is imperative to understand the variability of this intervention between different age groups. This knowledge may allow the optimization of neuromodulation protocols, allowing more careful and refined use in the clinic. The study primary outcomes is the difference between and within age groups on the variation of pre and post tDCS on pain threshold evaluated by Heath pain threshold on a Quantitative sensory testing paradigm and working memory performance evaluated by n-back test in healthy subjects of three age groups: adolescents, young adults, elderly. This is a randomized, single blinded, cross-over, sham-controlled clinical trial. The study will be conducted at the Clinical Research Center of the Hospital de Clínicas of Porto Alegre (HCPA). It will include 30 women, 10 women by age group: adolescents between 15 and 16 years,young adults between 30 and 40 years old and elderly women between 60 and 70 years. Participants will be randomized for a cross-over of three sessions: anodal stimulation in DLPFC, anodal stimulation in primary motor cortex (M1) as active control and sham stimulation.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
30
Inclusion Criteria
  • Age between 15 to 16 years for the adolescent group
  • Age between 30 to 40 years for the young adult group
  • Age between 60 to 70 years for the elderly group
  • From completed elementary school to incomplete superior education
  • right handed
Exclusion Criteria
  • Pregnancy
  • Current smoker or previous smoker within 10 years
  • Current Substance Use Disorder
  • Neurological condition (e.g., traumatic brain injury, stroke, brain tumor, epilepsy, brain surgery, brain implant)
  • Any diagnosed Psychiatric condition (e.g., Attention deficit/hyperactivity deficit (ADHD), bipolar disorder, major depressive disorder, schizophrenia, generalized anxiety disorder)
  • Use of any antidepressive or psychoactive, psychostimulant medication
  • Any chronic pain condition

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Sham tDCSSham tDCSParticipants will receive sham tDCS. The anode will be placed on the left DLPFC and the cathode on the over the right supra orbital area. The electrodes are 25cm², There will be a ram up and down of 30 seconds each, after the ramp up the current will be turned off.
Anodal tDCS on M1Anodal tDCS on M1Participants will receive anodal tDCS on the left M1 for 30 min duration, cathode will be placed over the right supra orbital area. The electrodes are 25cm², The stimulation current is 2 milliamperes (2mA).
Anodal tDCS on DLPFCAnodal tDCS on DLPFCParticipants will receive anodal tDCS on the left DLPFC for 30 mins duration, cathode will be placed over the right supra orbital area. The electrodes are 25cm², The stimulation current is 2 milliamperes (2mA).
Primary Outcome Measures
NameTimeMethod
Heat pain Thresholdpercentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session

Using the Quantitative sensory testing, this measure consists of the average temperature of 3 stimulus with increasing magnitude of heat where the participant presses a button to indicate when he/she first perceives pain.

Working memory performanceup to 60 minutes after tDCS onset

Working memory performance will be evaluated by a computerized n-back test associated with flankers at baseline and after each session of active tDCS (DLPFC or M1) or sham. The measure of performance is the D' discrimination index (calculated based on hit rate and false alarm rate).

Secondary Outcome Measures
NameTimeMethod
serum BDNF levelsup to 60 minutes before tDCS onset

Neuroplasticity biomarker will be assessed using serum brain-derived neurotrophic factor (BDNF) at baseline to be correlated with tdcs effects on primary outcomes

Inhibitory control performanceup to 60 minutes after tDCS onset

A computerized stop-signal task associated with flankers will evaluate inhibitory control. Performance index are calculated with the D' discrimination index (based on hits and false alarms for go and stop trials). The task will be performed at baseline and after the stimulation on each cross-over session.

Heat pain tolerancepercentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session

Using the Quantitative sensory testing, this measure consists of the temperature for a stimulus with increasing magnitude of heat where the participant presses a button to indicate the maximum heat tolerated.

Moderate painpercentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session

Using the Quantitative sensory testing, this measure consists of the average temperature of 3 stimulus with increasing magnitude of heat where the participant presses a button to indicate pain perceived at a moderate level, i.e. level of 6 in a numeric pain scale (0 to 10).

Area under the curve of the ERP during inhibitory control taskup to 60 minutes after tDCS onset

Area under the curve of the signal of event-related potential (ERP) evoked during the stop signal task with flankers (inhibitory control performance). The signal will be assessed using an 8 channel EEG device at baseline and after each cross-over session.

Alpha wave powerup to 60 minutes after tDCS onset

Assessment of alpha wave power (8Hz to 12Hz) will be done using an 8 channel EEG device during an "eyes-open and eyes-closed" paradigm where participant is in a resting state at baseline and after each cross-over session.

Beta wave powerup to 60 minutes after tDCS onset

Assessment of beta wave power (12Hz to 25Hz) will be done using an 8 channel EEG device during an "eyes-open and eyes-closed" paradigm where participant is in a resting state at baseline and after each cross-over session.

Heat thermal thresholdpercentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session

Using the Quantitative sensory testing, this measure consists of the average temperature of 3 stimulus with increasing magnitude of heat where the participant presses a button to indicate when he/she first perceives heat.

Theta wave powerup to 60 minutes after tDCS onset

Assessment of theta wave power (4Hz to 8Hz) will be done using an 8 channel EEG device during an "eyes-open and eyes-closed" paradigm where participant is in a resting state at baseline and after each cross-over session.

Unpleasantness sensationpercentual change from before the tDCS onset, to immediately after the end of tDCS application for each cross-over session

This measure will be assessed using a numeric pain scale (0 to 10 in which 0 represents no unpleasant sensation and 10 extremely unpleasant sensation) with which participant will indicate how unpleasant was the temperature of the quantitative sensory testing stimulus for the heat pain threshold.

Trial Locations

Locations (1)

Hospital de Clinicas e Porto Alegre (HCPA)

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Porto Alegre, Rio Grande Do Sul, Brazil

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