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

Evaluation of the Potentiating Effect of Transcranial Direct Current Stimulation (tDCS) on Opioid Analgesia of Pain Threshold in Humans

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 .

Study Overview

• Status: Unknown
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Remifentanil; Device: Active tDCS; Drug: Placebo; Device: Sham tDCS

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.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
      • Recruiting
      • Hospital de Clinicas e Porto Alegre (HCPA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remifentanil + Active 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.	Drug: Remifentanil; Remifentanil (IV infusion): 0,06mcg.kg.min. The infusion starts 10min before tDCSThe infusion will be stopped in the event of: a decrease in respiratory rate below 7 breaths / min, a peripheral oxygen saturation below 85%, a lower heart rate of 40 beats per minute, a lower mean arterial pressure of 60 mmHg, sedation causing inadequate management switch stimuli tests and occurrence of vomiting.; Device: Active tDCS; The stimulation will be administered with a pair of surface electrodes, sponge coated, soaked in saline. A battery-powered constant current stimulator will be used for this purpose (tDCS device). The stimulation is performed by placing the anodal electrode in the primary motor cortex (M1) and the cathodal one in the contralateral supraorbital area and it will use a 2 mA (milliampere) current.; Other Names: transcranial direct current stimulation
Other: Placebo + Active 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.	Device: Active tDCS; The stimulation will be administered with a pair of surface electrodes, sponge coated, soaked in saline. A battery-powered constant current stimulator will be used for this purpose (tDCS device). The stimulation is performed by placing the anodal electrode in the primary motor cortex (M1) and the cathodal one in the contralateral supraorbital area and it will use a 2 mA (milliampere) current.; Other Names: transcranial direct current stimulation; Drug: Placebo; Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.
Other: Remifentanil + Sham 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.	Drug: Remifentanil; Remifentanil (IV infusion): 0,06mcg.kg.min. The infusion starts 10min before tDCSThe infusion will be stopped in the event of: a decrease in respiratory rate below 7 breaths / min, a peripheral oxygen saturation below 85%, a lower heart rate of 40 beats per minute, a lower mean arterial pressure of 60 mmHg, sedation causing inadequate management switch stimuli tests and occurrence of vomiting.; Device: Sham tDCS; The 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.; Other Names: Sham - transcranial direct current stimulation
Other: Placebo + Sham 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.	Drug: Placebo; Saline infusion - Infusion 10min before the tDCS session, during the tDCS session and after the tDCS session, until the end of pain tests.; Device: Sham tDCS; The 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.; Other Names: Sham - transcranial direct current stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Thresholds of pain to the cold pressor test (CPT)	20min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of BDNF		20min
Intensity of electrical brain activity in the bi-spectral index (BIS)		60min
Sedation level in the visual analogue scale (VAS)		60min
Temperature of tolerance to the thermal stimulus (TTTS)		20min
Conditioned pain modulation (CPM)	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.	20min
Threshold of pain to the thermal stimulus (TT)		20min
Hemodynamic changes of brain using fNIRSNear-infrared spectroscopy (NIRS)	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.	60

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Wolnei Caumo, MD, P.h.D, Hospital de Clinicas de Porto Alegre - UFRGS

Publications and helpful links

General Publications

• Braulio G, Passos SC, Leite F, Schwertner A, Stefani LC, Palmer ACS, Torres ILS, Fregni F, Caumo W. Effects of Transcranial Direct Current Stimulation Block Remifentanil-Induced Hyperalgesia: A Randomized, Double-Blind Clinical Trial. Front Pharmacol. 2018 Feb 19;9:94. doi: 10.3389/fphar.2018.00094. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): April 1, 2016

Study Registration Dates

• First Submitted: April 6, 2015
• First Submitted That Met QC Criteria: April 28, 2015
• First Posted (Estimate): May 4, 2015

Study Record Updates

• Last Update Posted (Estimate): May 4, 2015
• Last Update Submitted That Met QC Criteria: April 28, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: tDCS; Pain; Opioid; Pain threshold
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: 14-0217