Cortical Neuroplasticity by Muscle Pain of Pain-induced Plasticity

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

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).

Study Overview

• Status: Completed
• Conditions: Exercise; Motor Activity; Hyperalgesia; Nerve Growth Factor; Abnormality of SSEPs
• Intervention / Treatment: Drug: Sterile solutions of recombinant human nerve growth factor (NGF)

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Nordjylland
    • Aalborg, Nordjylland, Denmark, 9000
      • Aalborg University

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
• 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aalborg University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 26, 2017
• Primary Completion (ACTUAL): February 28, 2018
• Study Completion (ACTUAL): February 28, 2018

Study Registration Dates

• First Submitted: November 19, 2017
• First Submitted That Met QC Criteria: November 26, 2017
• First Posted (ACTUAL): November 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 5, 2018
• Last Update Submitted That Met QC Criteria: March 2, 2018
• Last Verified: March 1, 2018

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; Sensation Disorders; Somatosensory Disorders; Myalgia; Hyperalgesia; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: N-20160022

Drug and device information, study documents

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