Repetitive Transcranial Magnetic Stimulation and the Development of Ongoing Muscle Pain

Study Overview
=================
Brief Summary
-----------------
The main purpose of the study is to assess the mechanisms of repeated sessions of repetitive trancranial magnetic stimulation (rTMS) applied on left dorsolateral prefrontal cortex on the development of pain in a prolonged muscle pain model.

Detailed Description
-----------------
This study aims to investigate whether i) rTMS of left DLPFC will reduce the severity and duration of experimentally induced muscle pain when a 5-day course of treatment is given immediately following an initial nerve growth factor (NGF) injection; ii) the analgesic effects of left DLPFC rTMS will be related to an improved cognitive network function as assessed by electroencephalography (EEG).

Official Title
-----------------
Repetitive Transcranial Magnetic Stimulation and the Development of Ongoing Muscle Pain

Conditions
-----------------
Pain Relief

Intervention / Treatment
-----------------
* Device: Repetitive trancranial magnetic stimulation (rTMS) group
* Device: Sham group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy men and women Speak and understand English. Exclusion Criteria: Pregnancy Drug addiction defined as the use of cannabis, opioids or other drugs Previous neurologic, musculoskeletal or mental illnesses Lack of ability to cooperate History of chronic pain or current acute pain Previous experience with rTMS Contraindications to rTMS application (history of epilepsy, metal in the head or jaw etc.). Failure to pass the TASS questionnaire (TASS = Transcranial Magnetic Stimulation Adult Safety Screen)

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Real treatment group<br>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. The coil produces small electric currents in the region of the brain just under the coil via electromagnetic induction. The protocol used in this research includes 20 minutes of 10Hz stimulation, 5 seconds on, 10 seconds off, at 110% RMT, for a total of 4000 pulses. | Device: Repetitive trancranial magnetic stimulation (rTMS) group<br>* Repetitive trancranial magnetic stimulation is applied on the dorsolateral prefrontal cortex. The protocol consists on 20 minutes of 10Hz stimulation, 5 seconds on, 10 seconds off, at 110% RMT, for a total of 4000 pulses.<br>|
| Sham Comparator: Sham treatment group<br>Sham coil is used to mimic the clicking sound of the TMS coil and skin stimulation | Device: Sham group<br>* A sham coil is used to mimic the clicking sound of the trancranial magnetic coil and skin stimulation.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain relief | Pain on an 11-point numerical rating scale (0 = no pain, 10 = most intense pain imaginable) | Change from baseline at 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle soreness | 7-point Likert scale; 0 = 'a complete absence of soreness', 1 = 'a light soreness in the muscle felt only when touched/vague ache', 2 = 'a moderate soreness felt only when touched/a slight persistent ache', '3 = 'a light muscle soreness when lifting or carrying objects', 4 = 'a light muscle soreness, stiffness or weakness when moving the wrist without gripping an object', 5 = 'a moderate muscle soreness, stiffness or weakness when moving the wrist', 6 = 'a severe muscle soreness, stiffness or weakness that limits the ability to move' | Change from baseline at 2 weeks | 
| Patient-rated Tennis Elbow Evaluation | The Patient-rated Tennis Elbow Evaluation will be used to assess average pain and disability of the injected arm | Change from baseline at 2 weeks | 
| Attention network test | This task assesses cognitive function in 3 domains: alerting, orienting, and executive function | Change from baseline at 2 weeks | 
| Pressure pain thresholds | Pressure applied to the surface of the skin using a handheld algometer. | Change from baseline at 2 weeks | 
| Cuff pressure algometry | The experimental setup consists of a tourniquet cuff, a computer-controlled air compressor and an electronic visual analog scale VAS (Aalborg University, Denmark). The cuff is connected to the compressor and wrapped around the leg. The pain intensity is recorded with the electronic VAS and sampled at 10 Hz. The 0 cm and 10 cm extremes on the VAS are defined as no pain and as maximal pain, respectively. The compression rate of the cuff is programmed on and controlled by a computer. | Change from baseline at 2 weeks | 
| EEG recordings | we will record brain activity in the following conditions: eyes closed rest, performance of a computer-based cognitive task (ANT). | Change from baseline at 1 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nerve growth factor, repetitive transcranial magnetic stimulation, dorsolateral prefrontal cortex