An Exploration of the Neuroplasticity of Endogenous Analgesia in Health and Chronic Pain

Study Overview
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Brief Summary
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Transcranial magnetic stimulation (TMS) is a neurophysiological tool for studying cortical functions, and in addition, has an analgesic therapeutic effect whose underlying mechanism is unknown. The proposed research will use TMS in conjunction with brain imaging and electrophysiology to examine cortical plasticity and connectivity modifications induced by repetitive TMS (rTMS) targeted to affect cortical regions associated with endogenous analgesia (EA). This will be carried out in both healthy and chronic pain (fibromyalgia) states. rTMS analgesic intervention, targeted to the motor cortex (M1) will be preceded and followed by structural and functional magnetic resonance imaging (fMRI), and Diffusion Tensor Imaging (DTI). This will be done in order to examine alterations of cortical and brainstem mechanisms involved in EA and to investigate connectivity changes between cortical and sub-cortical regions of the EA networks. The latter as well as EA efficiency and pain-related personality variables will be used to assess individual differences in neuroplasticity within the EA systems in both healthy subjects and chronic pain patients.

Detailed Description
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Transcranial magnetic stimulation (TMS) is a neurophysiological tool for studying cortical functions, and in addition, has an analgesic therapeutic effect whose underlying mechanism is unknown. The proposed research will use TMS in conjunction with brain imaging and electrophysiology to examine cortical plasticity and connectivity modifications induced by repetitive TMS (rTMS) targeted to affect cortical regions associated with endogenous analgesia (EA). This will be carried out in both healthy and chronic pain (fibromyalgia) states. rTMS analgesic intervention, targeted to the motor cortex (M1) will be preceded and followed by structural and functional magnetic resonance imaging (fMRI), and Diffusion Tensor Imaging (DTI). This will be done in order to examine alterations of cortical and brainstem mechanisms involved in EA and to investigate connectivity changes between cortical and sub-cortical regions of the EA networks. The latter as well as EA efficiency and pain-related personality variables will be used to assess individual differences in neuroplasticity within the EA systems in both healthy subjects and chronic pain patients .

Official Title
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Integration of Neuroimaging and Transcranial Magnetic Stimulation: an Exploration of the Neuroplasticity of Endogenous Analgesia in Health and Chronic Pain

Conditions
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Fibromyalgia

Intervention / Treatment
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* Device: active repeated transcranial magnetic stimulation
* Device: 'sham' repeated transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a prior FMS diagnosis by a rheumatologist or pain specialist based on American College of Rheumatology (ACR) preliminary diagnostic criteria for fibromyalgia healthy subjects - no pain/psychiatry/neurological diseases Exclusion Criteria: other chronic pain, psychiatric or neurological diseases. All will be asked to withdraw from any pain-relieving medications for 24h before the testing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active rTMS<br>active repeated transcranial magnetic stimulation over primary motor cortex along 5-10 daily sessions | Device: active repeated transcranial magnetic stimulation<br>* ten daily sessions with active 10Hz 20 min-long stimulation over the primary motor cortex<br>|
| Sham Comparator: 'sham' rTMS<br>'sham' repeated transcranial magnetic stimulation over primary motor cortex along 5-10 daily sessions | Device: 'sham' repeated transcranial magnetic stimulation<br>* ten daily sessions with 'sham' 10Hz 20 min-long stimulation over the primary motor cortex<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rTMS-induced change in fibromyalgia pain level | Fibromyalgia pain level will be measured using the numerical pain scale; the patients will be asked to rate their mean pain level over the last 5 days | through study completion, an average of 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment-induced changes of white-matter connectivity of the brain | White-matter connectivity will be measured using the method of diffusion tensor imaging of the brain | through study completion, an average of 2 year |