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Evaluation of the Potentiating Effect of tDCS on Opioid Analgesia of Pain Threshold in Humans

Phase 2
Conditions
Acute Pain
Interventions
Device: Active tDCS
Device: Sham tDCS
Drug: Placebo
Registration Number
NCT02432677
Lead Sponsor
Hospital de Clinicas de Porto Alegre
Brief Summary

The purpose of this study is to evaluate the potential additive effect of tDCS compared to placebo-sham in opioid analgesia on pain thresholds in nociceptive experimental model in healthy volunteers .

Detailed Description

Pain is a prevalent symptom in medicine and the role of various opioids is valuable in the treatment of moderate to severe pain. Several technologies of brain stimulation , including transcranial direct current stimulation ( tDCS) are emerging as therapeutic options for many pain conditions. The effect of tDCS was demonstrated in sensory perception , decreasing the threshold for acute pain in healthy volunteers and in various chronic pain conditions . There is evidence about the use of tDCS with the participation through many mechanisms in cortical modulation , including the regulation of neurotransmitters, including opioids. In the context of neurostimulation, opioidergic system and cortical pain modulation, emerge the hypothesis of a possible potentiating effect of tDCS on clinical application of opioid analgesia.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Male
Target Recruitment
48
Inclusion Criteria
  • Male
  • 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 sleep disorders (apnea, hypersomnia, somnambulism...)
  • History of alcohol or substance abuse
  • Neurological disorder
  • Use of anti-inflammatory drugs, steroids and non-steroids, opioid and non-opioid analgesics, psychiatric medications, anticonvulsants, alpha and beta blockers
  • Traumatic brain injury
  • Neurosurgery
  • Metallic implant in the brain

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + Active tDCSActive tDCS* tDCS session: the procedure will initiate by placing an anode electrode on the primary motor cortex (contralateral to the dominant cortex) and the cathode electrode on the contralateral supra-orbital region. The current employed is 2mA of transcranial direct-current stimulation administered for 20 minutes. * Placebo: Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Remifentanil + Active tDCSActive tDCS* tDCS session: the procedure will initiate by placing an anode electrode on the primary motor cortex (contralateral to the dominant cortex) and the cathode electrode on the contralateral supra-orbital region. The current employed is 2mA of transcranial direct-current stimulation administered for 20 minutes. * Remifentanil - 0,06mcg.kg.min - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Remifentanil + Sham tDCSSham tDCS* Sham tDCS: consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session. * Remifentanil - 0,06mcg.kg.min - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Placebo + Sham tDCSSham tDCS* Sham tDCS: consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session. * Placebo: Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Placebo + Active tDCSPlacebo* tDCS session: the procedure will initiate by placing an anode electrode on the primary motor cortex (contralateral to the dominant cortex) and the cathode electrode on the contralateral supra-orbital region. The current employed is 2mA of transcranial direct-current stimulation administered for 20 minutes. * Placebo: Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Placebo + Sham tDCSPlacebo* Sham tDCS: consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session. * Placebo: Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Remifentanil + Active tDCSRemifentanil* tDCS session: the procedure will initiate by placing an anode electrode on the primary motor cortex (contralateral to the dominant cortex) and the cathode electrode on the contralateral supra-orbital region. The current employed is 2mA of transcranial direct-current stimulation administered for 20 minutes. * Remifentanil - 0,06mcg.kg.min - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Remifentanil + Sham tDCSRemifentanil* Sham tDCS: consists in the same montage of the active tDCS, but the device is turned off 30 seconds after starting stimulation (without letting the patient notice it). The rest of the montage is kept identical to the active one during the 20 minutes session. * Remifentanil - 0,06mcg.kg.min - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Primary Outcome Measures
NameTimeMethod
Thresholds of pain to the cold pressor test (CPT)20min
Secondary Outcome Measures
NameTimeMethod
Serum levels of BDNF20min
Threshold of pain to the thermal stimulus (TT)20min
Intensity of electrical brain activity in the bi-spectral index (BIS)60min
Sedation level in the visual analogue scale (VAS)60min
Conditioned pain modulation (CPM)20min

A nociceptive tonic conditioning stimulus - immersion of the non-dominant hand in cold water (0°C for 1 minute) - will be applied concomitant to the progressive thermal stimulus in the dominant forearm as applied in the QST pattern until it reaches the 6/10 pain temperature previously determined by the participant.

Temperature of tolerance to the thermal stimulus (TTTS)20min
Hemodynamic changes of brain using fNIRSNear-infrared spectroscopy (NIRS)60

The vascular response will be assessed using functional near infrared spectroscopy (fNIRS). Emerging technique that allows the functional mapping of the brain, with a better understanding of the neuro-vascular coupling, the neurophysiological fluctuations and cerebral hemodynamics.

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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