Modulation of an Experimental Prolonged Pain Model Using High Definition Transcranial Direct Current Stimulation

The purpose of this double-blinded, parallel group randomized controlled trial is to investigate the effects of high definition transcranial direct current stimulation (HD-tDCS) on an experimental prolonged pain model in healthy subjects.

Study Overview

• Status: Unknown
• Conditions: Healthy; Pain, Muscle
• Intervention / Treatment: Device: Active HD-tDCS; Device: Sham HD-tDCS

Detailed Description

The purpose of this double-blinded, parallel group randomized controlled trial is to investigate the effects of high definition transcranial direct current stimulation (HD-tDCS) on an experimental prolonged pain model in healthy subjects. Forty healthy participants are administered the compound Nerve Growth Factor (NGF) in the right first dorsal interosseous muscle (FDI), which produced prolonged muscle soreness and hyperalgesia.

The forty participants are randomly allocated to either the control group receiving a Sham-tDCS paradigm, or the intervention group receiving three consecutive days of multimodal HD-tDCS targeting primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) simultaneously.

The somatosensory profile is assessed at baseline, before administration of NGF as well as prior and post each HD-tDCS session using standardised quantitative sensory testing.

It is hypothesised that the active HD-tDCS will modulate the neurological changes induced by the experimental pain condition, which will alleviate the hyperalgesia and hypersensitivity.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sebastian Kold, MSc; Phone Number: +4522850345; Email: sks@hst.aau.dk

Study Locations

• Denmark
  • Nordjylland
    • Aalborg, Nordjylland, Denmark, 9000
      • Recruiting
      • Center for Neuroplasticity and Pain
      • Contact: Thomas Graven-Nielsen, Prof.; Phone Number: +45 2216 049; Email: tgn@hst.aau.dk

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 men and women.
• Able to speak, read and understand English or Danish.

Exclusion Criteria:

• Pregnancy
• Drug addiction defined as the use of cannabis, opioids or other drugs
• Current use of opioids, antipsychotics, benzodiazepines
• Previous or current neurological, musculoskeletal, rheumatic, malignant, inflammatory or mental illnesses
• Current or prior chronic pain conditions
• Lack of ability to cooperate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active tDCS; Both groups will receive an injection with 5 μg (0.5 ml) Nerve Growth Factor (NGF) in the first dorsal interosseous muscle (FDI muscle) prior to the HD-tDCS intervention. This injection a pain model, that is intended to induce muscle soreness and hyperalgesia.	Device: Active HD-tDCS; Using the Starstim 32, HD-tDCS equipment we provide 20 minutes of 2 mA anodal multimodal stimulation of dorsolateral prefrontal cortex (DLPFC) and primary motor cortex simultaneously using ring-cathode configurations around the two anodes.
PLACEBO_COMPARATOR: Sham tDCS; Both groups will receive an injection with 5 μg (0.5 ml) Nerve Growth Factor (NGF) in the first dorsal interosseous muscle (FDI muscle) prior to the HD-tDCS intervention. This injection a pain model, that is intended to induce muscle soreness and hyperalgesia.	Device: Sham HD-tDCS; Using the Starstim 32, HD-tDCS equipment we provide sham stimulation with 30 seconds of ramping up to 2 mA intensity, then turning off for 19 minutes and then ramping down from 2 mA intensity to 0 in the last 30 seconds. This sham-configuration is intended to mimic the sensory experience of active HD-tDCS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pressure pain threshold.	A hand-held pressure algometer (Somedic, Hörby, Sweden) with a 1-cm2 probe will be used to record the pressure pain threshold. The pressure is increased gradually at a rate of 20 kPa/s. The measurement is repeated three times on the first dorsal interosseous muscle.	Six assessments over three days: Baseline is assessed before any intervention at day one, and then the pain thresholds are assessed before and after each intervention on the subsequent two days.
Change in pressure pain tolerance.	A hand-held pressure algometer (Somedic, Hörby, Sweden) with a 1-cm2 probe will be used to record the pressure pain threshold at baseline. The pressure is increased gradually at a rate of 20 kPa/s. The measurement is repeated three times on the first dorsal interosseous muscle. The participant is asked to rate the pain on a numerical rating scale (NRS) from 0-10. 0 representing no pain at all, and 10 representing the worst pain imaginable.	Six assessments over three days: Baseline is assessed before any intervention at day one, and then the pain thresholds are assessed before and after each intervention on the subsequent two days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in tactile detection threshold	Tactile threshold will be measured using an anaesthesiometer consisting of a set of Von Frey filaments. The filaments are made of nylon fibre of various diameters so as to provide a range of forces of up to 300 grams. The minimum force that the subject can detect will be identified. This will be assessed on flexor carpi radialis on the right hand arm.	Six assessments over three days: Baseline is assessed before any intervention at day one, and then the sensory thresholds are assessed before and after each intervention on the subsequent two days.
Change in mechanical pain threshold	Mechanical pain threshold (MPT) will be measured using a set of weighted pinprick stimulators with a flat contact area of 0.25 mm diameter that exert forces between 8 and 512 mN. Threshold procedures will use a method of limits with up to five series of ascending and descending stimulus intensities. This will be assessed on flexor carpi radialis on the right hand arm.	Six assessments over three days: Baseline is assessed before any intervention at day one, and then the sensory thresholds are assessed before and after each intervention on the subsequent two days.
Change in conditioned pain modulation (CPM)	A computer-controlled cuff pressure algometer (Nocitech, Denmark) with an air-filled tourniquet cuff (VBM, Germany) will be used to record cuff pressure-induced pain thresholds over the muscle bulk on the calfs. The pressure is increased gradually at a rate of 1 kPa/s to assess pain tolerance on a 0-10 VAS scale, where 0 is no pain at all and 10 is the worst pain imaginable. During CPM testing, the pain tolerance is first assessed on one leg marking the baseline. The pressure pain tolerance is then assessed on the same leg again, while the contralateral calf is applied a simultaneous painful pressure stimulus. The outcome of the CPM testing is the difference in pressure pain tolerance measured in kPA between the first and the second assessment. The larger the positive difference is between the baseline and the second assessment, the stronger CPM effect the subject has.	Three assessments over three days: Baseline is assessed before the stimulation at day one, and then again after the stimulation on the two subsequent days.
Change in temporal summation of pain (TSP).	TSP will be applied using cuff pressure algometry. A total of 10 repeated mechanical pressure stimuli will be delivered at 0.5 Hz (1-s stimuli duration and 1-s interval between stimuli) to the test area. During the 10 repeated stimuli, subjects will continuously rate the pain intensity on a 10-cm continuous VAS. TSP is assessed on the calf of the right leg.	Three assessments over three days: Baseline is assessed before the stimulation at day one, and then again after the stimulation on the two subsequent days.
Change in electroencephalography response (EEG).	EEG will be recorded for four minutes prior to the HD-tDCS, during the HD-tDCS and four minutes immediately after the HD-tDCS. In the four minutes before and after HD-tDCS, the subject will have their eyes open for two minutes and their eyes closed for two minutes. The EEG data will be analyzed with a focus on the resting state. In particular the Alpha frequency brain waves are of interest, but exploratory analysis will be conducted on the Beta, Theta and Gamma frequency bands as well.	Three assessments over three days: The EEG will be recorded as a part of the HD-tDCS intervention.

Collaborators and Investigators

• Sponsor: Aalborg University
• Collaborators: Danish National Research Foundation
• Investigators: Principal Investigator: Thomas Graven-Nielsen, Prof., Aalborg University

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2020
• Primary Completion (ANTICIPATED): February 1, 2021
• Study Completion (ANTICIPATED): April 29, 2021

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (ACTUAL): December 2, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 2, 2020
• Last Update Submitted That Met QC Criteria: December 1, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Myalgia
• Other Study ID Numbers: N-20180085.p2

Drug and device information, study documents

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