Daily Sessions of rTMS to the Left DLPFC Modulate the Pain Thresholds and CPM

Can Daily Sessions of rTMS to the Left DLPFC Boost Diffuse Noxious Inhibitory Control and Pain Thresholds in Healthy Subjects

The main purpose of the study is to assess whether repeated sessions of repetitive trancranial magnetic stimulation (rTMS) applied on left dorsolateral prefrontal cortex main boost the pain thresholds.

Study Overview

• Status: Completed
• Conditions: Pain Relief
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation

Detailed Description

Pain is the largest health-related burden on society and, despite many decades of pain research, there are still few effective treatments. Since pain experience is a construct of the central nervous system (CNS), chronic pain has been recently thought to be a CNS disorder.

Repetitive transcranial magnetic stimulation (rTMS) is a safe, non-invasive technique for cerebral cortex stimulation and the clinical applications of which have expanded considerably in recent years. Recent studies have been shown that 'classical' rTMS to different cortical areas temporary reduce chronic and acute pain, suggesting that rTMS may ´have some clinical application in future management of chronic pain. However, new rTMS paradigms involving theta burst stimulation (TBS) have recently been described with the major clinical advantage to be much shorter than 'classical' rTMS. The investigators hypothesize that cTBS would yield analgesic effects similar to or, possibly, even stronger than those produced by 'classical' rTMS. The investigators will carry out a sham-controlled, randomized, double-blind, crossover study in healthy volunteers, to compare the analgesic effects of two rTMS protocols over dorsolateral prefrontal cortex: classical high-frequency rTMS (10 Hz), and TBS. As rTMS-induced analgesia may be dependent on changes in pain modulatory systems, the investigators will analyze the effects of the stimulation on conditioned pain modulation (CPM). More specifically, the investigators will compare the effects of multiple sessions of rTMS on the inhibition of a test experimental stimulus induced by heterotopic noxious stimuli, to assess possible changes in diffuse noxious inhibitory controls.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Enrico De Martino
  • Nordjylland
    • Aalborg, Nordjylland, Denmark, 9000
      • Enrico De Martino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Major medical conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cTBS group; Transcranial magnetic stimulation (TMS) is used to stimulate small regions of the brain. During a TMS procedure, a magnetic field generator, or "coil", is placed near the head of the person receiving the treatment. TBS refers to a rTMS protocol where pulses are applied in bursts of three, delivered at a frequency of 50 Hz and an inter-burst interval of 200 ms (5 Hz).	Device: repetitive transcranial magnetic stimulation; Repetitive transcranial Magnetic Stimulation (rTMS) can be used to temporary modify the brain activity.
Active Comparator: High frequenct rTMS group; High frequency refers to a rTMS protocol where pulses are applied in at 10Hz frequency	Device: repetitive transcranial magnetic stimulation; Repetitive transcranial Magnetic Stimulation (rTMS) can be used to temporary modify the brain activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure pain thresholds (PPT)	Pressure will be applied at a rate of 30 kPa/s perpendicularly to the surface of the skin using a handheld algometer (1-cm2 probe; Somedic, Hörby, Sweden). Three readings at the pressure pain threshold (PPT) will be made at 1-minute intervals, at four sites; i) right elbow, ii) left elbow, iii) right leg and iv) left leg. The data will be reported in kPa.	The study comprises two interventions of four experimental sessions on consecutive days (Day-1 to Day-4). Changes from Day-1 at Day-4 will be investigated.
Cold pain thresholds, heat pain thresholds and supra-thresholds painful stimuli	The temperature of the thermode is slowly decreased or increased to the maximum tolerable levels. The participant will click a button as soon as the tolerable level has been reached, which will bring the temperature back to baseline 32 degrees Celsius. Thresholds are determined by raising or dropping the temperature slowly from baseline skin temperature until the participant reports feeling of pain. The experimenter will then determine the temperature that is consistently rated as moderately painful by applying a temperature above the threshold level and asking the participant to rate the pain from 0 (no pain) to 10 (most intense pain imaginable).	The study comprises two interventions of four experimental sessions on consecutive days (Day-1 to Day-4). Changes from Day-1 at Day-4 will be investigated.
Condition pain modulation (supra-thresholds painful stimuli ): visual analogue scale (VAS: 0-100mm)	First, the volunteers will immerse the left hand in a bucket with water and ice at 4° C for around 45-60 seconds to reach a VAS pain of 60-70/100mm. Immediately after, supra-thresholds painful stimuli over the right leg will be repeated in a randomized order. The supra-thresholds painful stimuli will be reported in a VAS scale (from 0 to 10).	The study comprises two interventions of four experimental sessions on consecutive days (Day-1 to Day-4). Changes from Day-1 at Day-4 will be investigated.
Condition pain modulation (pressure pain thresholds): visual analogue scale (VAS: 0-100mm)	First, the volunteers will immerse the left hand in a bucket with water and ice at 4° C for around 45-60 seconds to reach a VAS pain of 60-70/100mm. Immediately after, pressure pain thresholds over the right leg will be repeated. The pressure pain thresholds will be reported in kPa.	The study comprises two interventions of four experimental sessions on consecutive days (Day-1 to Day-4). Changes from Day-1 at Day-4 will be investigated.

Collaborators and Investigators

• Sponsor: Aalborg University

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2018
• Primary Completion (Actual): December 15, 2018
• Study Completion (Actual): December 15, 2018

Study Registration Dates

• First Submitted: November 2, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (Actual): November 7, 2018

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: December 15, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: repetitive transcranial magnetic stimulation; pain thresholds; dorsolateral prefrontal cortex
• Other Study ID Numbers: 54271916.8.0000.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No