Cortical Neuroplasticity by Muscle Pain of Pain-induced Plasticity

Study Overview
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Brief Summary
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The purpose of this study is to investigate the sensory-motor cortical excitability response to delayed onset muscle soreness (DOMS) on Extensor Carpi Radialis (ECR) muscle during muscle hyperalgesia provoked by nerve growth factor (NGF).

Detailed Description
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The purpose of this study is to assess changes in sensory-motor cortical excitability during experimental muscle hyperalgesia across several days provoked by injections of nerve growth factor (NGF) into the Extensor Carpi Radialis (ECR) muscle and delayed onset muscle soreness (DOMS) of the ECR muscle. It was hypothesized that muscle hyperalgesia across several days would result in: i) Increased sensory cortical excitability, based on somatosensory evoked potentials by means of electrical stimulation of the radial nerve, (increase of central-parietal evoked-potential P45 and decrease of frontal evoked-potential N30); ii) Increased corticomotor excitability of a ECR (increase map volume and number of active sites), assessed as motor evoked potentials induced by transcranial magnetic stimulation in primary motor cortex (M1); iii) Reduction of alpha oscillation based on nociceptive stimulus-evoked suppression of alpha activity in sensory regions (recording electrodes on contra-lateral parietal area);

Official Title
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Cortical Neuroplasticity by Muscle Pain and Non-invasive Modulation of Pain-induced Plasticity

Conditions
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Nerve Growth Factor, Exercise, Motor Activity, Abnormality of SSEPs, Hyperalgesia

Intervention / Treatment
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* Drug: Sterile solutions of recombinant human nerve growth factor (NGF)


Participation Criteria
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Eligibility Criteria
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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
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nerve growth factor group<br>Three injections of sterile solutions of recombinant human nerve growth factor (NGF) will be performed in the right extensor carpi radialis muscle to induce muscle hyperalgesia. | Drug: Sterile solutions of recombinant human nerve growth factor (NGF)<br>* The intramuscular injections of NGF cause muscle soreness.<br>|
| Experimental: Nerve growth factor group + delayed onset muscle soreness<br>Injections of nerve growth factor and eccentric exercise of the extensor carpi radialis muscle will be performed to induce muscle hyperalgesia. | Drug: Sterile solutions of recombinant human nerve growth factor (NGF)<br>* The intramuscular injections of NGF cause muscle soreness.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain rating | 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 | 
| Pressure pain thresholds | Pressure applied to the surface of the skin using a handheld algometer. | Change from baseline at 2 weeks | 
| Motor evoked potentials | Transcranial magnetic stimualtion will be used to evoke motor evoked potentials (MEPs) to the extensor carpi radialis muscle | Change from baseline at 1 week | 
| Sensory evoked potentials | EEG recodring | Change from baseline at 1 week | 
| Alpha oscillations | Continuous EEG recording | Change from baseline at 1 weeks |