Cortical Plasticity After Motor Cortex Stimulation in Healthy Subject and Chronic Pain Patients

Study Overview
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Brief Summary
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The primary aim of this study is to evaluate the induction of sensory-motor cortex plasticity after motor cortex stimulation in healthy subjects, using laser-evoked nociceptive cortical potentials, and in chronic neuropathic pain patients using functional MRI. As a secondary goal, the project will analyse possible correlations between the magnitude of cortical plasticity and that of the pain-relieving effect. In healthy subjects, cortical plasticity is evaluated by the comparison of somatosensory cortical maps before and after two isolated sessions of 20 Hz and theta-burst rTMS, in a cross-over randomized study. Two sessions of 5 consecutive days of rTMS are proposed to the patients with a minimum of 4 weeks between the two sessions, defined by 20 Hz and theta-burst stimulation in a cross-over randomized order. Cortical plasticity of the motor cortex is evaluated via functional MRI (motor activation) performed before the first rTMS session and the last day of each session of rTMS.

Official Title
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Study of Sensory-motor Cortex Plasticity After Motor Cortex Stimulation in Healthy Subject and Chronic Pain Patients

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy subjects aged from 18 to 70 years, male or female, with social protection, fully informed and having given their written consent. patients : aged from 18 to 80 years, male or female, with social protection , fully informed and having given their written consent. unilateral pharmacoresistant neuropathic pain during at least one year, without any change of the pharmacological treatment since at least one month Exclusion Criteria: for healthy subjects only: history of chronic pain analgesic medication within 24h before stimulation For patients only: new analgesic treatment within 1 month before consent for both: drug addiction, headache, epilepsy history ferromagnetic intracranial device implanted stimulator absence of contraceptive method for women of childbearing age

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: healthy volunteers<br> | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* 20Hz and Theta Burst stimulation, both at 80% of motor threshold in contralateral intrinsic hand muscles. Five consecutive days of each mode of stimulation, separated by a minimum of 4 weeks. Daily self-monitoring of pain, sleep quality and fatigue by mans of a 10-item questionnaire<br>|
| Experimental: Patients with resistant pain<br> | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* 20Hz and Theta Burst stimulation, both at 80% of motor threshold in contralateral intrinsic hand muscles. Five consecutive days of each mode of stimulation, separated by a minimum of 4 weeks. Daily self-monitoring of pain, sleep quality and fatigue by mans of a 10-item questionnaire<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cortical plasticity induced by rTMS - - Somatosensory evoked potentials | Assessment of plastic changes induced in sensori-motor cortex by the application of repetitive magnetic stimulation in healthy subjects and chronic pain patients. In healthy subjects, mapping of cortical responses amplitude and source reconstruction techniques (dipole modelisation, BESA) before / after a single rTMS session In chronic pain patients, contrast analysis between extent and location of motor activations (to hand, foot and mouth contraction) before / after one week of daily rTMS, analysed with Statistical Parametric Mapping (SPM12) | just before the isolated 20 Hz or theta-burst stimulation for healthy subjects | 
| cortical plasticity induced by rTMS - - Somatosensory evoked potentials | Assessment of plastic changes induced in sensori-motor cortex by the application of repetitive magnetic stimulation in healthy subjects and chronic pain patients. In healthy subjects, mapping of cortical responses amplitude and source reconstruction techniques (dipole modelisation, BESA) before / after a single rTMS session In chronic pain patients, contrast analysis between extent and location of motor activations (to hand, foot and mouth contraction) before / after one week of daily rTMS, analysed with Statistical Parametric Mapping (SPM12) | just after the isolated 20 Hz or theta-burst stimulation for healthy subjects | 
| cortical plasticity induced by rTMS -- fMRI | Assessment of plastic changes induced in sensori-motor cortex by the application of repetitive magnetic stimulation in healthy subjects and chronic pain patients. In healthy subjects, mapping of cortical responses amplitude and source reconstruction techniques (dipole modelisation, BESA) before / after a single rTMS session In chronic pain patients, contrast analysis between extent and location of motor activations (to hand, foot and mouth contraction) before / after one week of daily rTMS, analysed with Statistical Parametric Mapping (SPM12) | within 1 week before the first day of stimulation (20 Hz or theta-burst) for the patients | 
| cortical plasticity induced by rTMS -- fMRI | Assessment of plastic changes induced in sensori-motor cortex by the application of repetitive magnetic stimulation in healthy subjects and chronic pain patients. In healthy subjects, mapping of cortical responses amplitude and source reconstruction techniques (dipole modelisation, BESA) before / after a single rTMS session In chronic pain patients, contrast analysis between extent and location of motor activations (to hand, foot and mouth contraction) before / after one week of daily rTMS, analysed with Statistical Parametric Mapping (SPM12) | after the 5th day of stimulation (20 Hz or theta-burst) for the patients | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nonparametric (Chi-2) contrast of dichotomized pain reports before/after rTMS and extent of fMRI activation change (also dichotomized) MRI T1 3D and T2* |  | within 1 week before the first day of stimulation Stats after 40 patients studied. | 
| Nonparametric (Chi-2) contrast of dichotomized pain reports before/after rTMS and extent of fMRI activation change (also dichotomized) MRI T1 3D and T2* |  | after the 5th day of stimulation. Stats after 40 patients studied. | 
| Linear and nonlinear correlation between the magnitude of induced cortical plasticity and the magnitude of pain relief induced by rTMS. MRI T1 3D and T2*, |  | within 1 week before the first day of stimulation Stats after 40 patients studied. | 
| Linear and nonlinear correlation between the magnitude of induced cortical plasticity and the magnitude of pain relief induced by rTMS. MRI T1 3D and T2*, |  | after the 5th day of stimulation. Stats after 40 patients studied. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuropathic Pain, Stimulation of the Motor Cortex (SCM), Pharmacoresistant, rTMS