Cortical Neuroplasticity by Muscle Pain of Pain-induced Plasticity

• ClinicalTrials.gov Identifier: NCT03354624
• Recruitment Status: Completed
• First Posted: November 28, 2017
• Last Update Posted: March 5, 2018
• Sponsor: Aalborg University
• Information provided by (Responsible Party): Enrico De Martino, Aalborg University

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Nerve Growth Factor; Exercise; Motor Activity; Abnormality of SSEPs; Hyperalgesia	Drug: Sterile solutions of recombinant human nerve growth factor (NGF)	Not Applicable

Detailed Description:

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);

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Cortical Neuroplasticity by Muscle Pain and Non-invasive Modulation of Pain-induced Plasticity
• Actual Study Start Date: November 26, 2017
• Actual Primary Completion Date: February 28, 2018
• Actual Study Completion Date: February 28, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nerve growth factor group; 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); The intramuscular injections of NGF cause muscle soreness.
Experimental: Nerve growth factor group + delayed onset muscle soreness; 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); The intramuscular injections of NGF cause muscle soreness.

Outcome Measures

Primary Outcome Measures :

1. Pain rating [ Time Frame: Change from baseline at 2 weeks ]
   Pain on an 11-point numerical rating scale (0 = no pain, 10 = most intense pain imaginable)

Secondary Outcome Measures :

1. Muscle soreness [ Time Frame: Change from baseline at 2 weeks ]
   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'
2. Patient-rated Tennis Elbow Evaluation [ Time Frame: Change from baseline at 2 weeks ]
   The Patient-rated Tennis Elbow Evaluation will be used to assess average pain and disability of the injected arm
3. Pressure pain thresholds [ Time Frame: Change from baseline at 2 weeks ]
   Pressure applied to the surface of the skin using a handheld algometer.
4. Motor evoked potentials [ Time Frame: Change from baseline at 1 week ]
   Transcranial magnetic stimualtion will be used to evoke motor evoked potentials (MEPs) to the extensor carpi radialis muscle
5. Sensory evoked potentials [ Time Frame: Change from baseline at 1 week ]
   EEG recodring
6. Alpha oscillations [ Time Frame: Change from baseline at 1 weeks ]
   Continuous EEG recording

Eligibility Criteria

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

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)

Contacts and Locations

Locations

Denmark

Aalborg University

Aalborg, Nordjylland, Denmark, 9000

Sponsors and Collaborators

Aalborg University

More Information

• Responsible Party: Enrico De Martino, Medical Doctor, Aalborg University
• ClinicalTrials.gov Identifier: NCT03354624 History of Changes
• Other Study ID Numbers: N-20160022
• First Posted: November 28, 2017
• Last Update Posted: March 5, 2018
• Last Verified: March 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Myalgia; Hyperalgesia; Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Pain; Mitogens; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action