Central Mechanisms of Chronic Pain and Fatigue Subtitle: Functional Imaging of Brain and Spinal Cord

Study Overview
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Brief Summary
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Chronic pain and fatigue are characterized by peripheral and central mechanisms including low pain thresholds, temporal summation, peripheral and central sensitization. This application will focus on central factors of chronic pain and fatigue. Functional brain imaging will be used to characterized brain and spinal cord abnormalities that contribute to the mechanisms of these disorders.

Detailed Description
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Chronic fatigue (ME/CFS) and fibromyalgia syndrome (FM) are a chronic musculoskeletal pain disorder that predominantly afflicts women. Frequently associated insomnia, cognitive abnormalities, and fatigue may lead to early disability. No consistent soft tissue abnormalities have been identified so far in these patients. The cause of these disorders is unknown, no highly effective treatment is available and the current methods of diagnosis are imprecise and unreliable. The Investigators previously used quantitative sensory testing to improve upon diagnoses of these disorders by supplementing the current procedure of manipulating defined pressure points by hand and noting the presence or absence of pain. The quantitative methods of evaluation involve repetitive application of brief, non-injurious thermal/mechanical stimulation that normally produces a moderate degree of temporal summation of sensation intensity. The patients and normal control subjects will verbally rate the magnitude of late sensations elicited by each stimulus, using a numerical scale. Chronic pain in these patients results, at least partially, from exaggerated activation of central N-methyl-D-aspartate (NMDA) receptors as a result of enhanced input from unmyelinated peripheral afferent nerve fibers supplying deep tissues. Temporal summation of second pain can lead to central sensitization with subsequent signs of hyperalgesia and allodynia. Functional brain imaging of ME/CFS and FM patients, as proposed in this study, will be used to document their ratings of repetitive experimental stimuli and the resulting pain augmentation. Successful completion of this study will provide a new method for the evaluation of chronic pain/fatigue mechanism and their response to therapy.

Official Title
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Central Mechanisms of Chronic Pain and Fatigue Subtitle: Functional Imaging of Brain and Spinal Cord

Conditions
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Chronic Fatigue Syndrome, Fibromyalgia

Intervention / Treatment
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* Device: A Peltier for Sensory testing
* Device: functional magnetic resonance imaging for Brain Neuroimaging
* Device: fMRI for Spinal Cord Neuroimaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of FM will require a history of chronic widespread pain as well as the presence of at least eleven out of eighteen paired tender points. diagnosis of ME/CFS will require a history of chronic fatigue persisting or relapsing for more than 6 months as well as the presence of at least four out of eight designated symptoms. willing to reduce anti-depressants to low levels like amitriptyline 10 mg/day, trazodone 50 mg/day, citalopram 20 mg/day, for at least five half-lives of the medication. Exclusion Criteria: Patients unwilling or unable to discontinue or modify analgesics, hypnotics, anxiolytics, or anti-depressants during the study period will be excluded from this trial.

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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Control<br>normal volunteers (HC) Undergoing sensory testing, brain and spinal cord neuroimaging and Inventory assessments. | Device: A Peltier for Sensory testing<br>* Subjects will be trained to rate the magnitude of late sensations elicited following brief (700 msec) contact of a preheated thermode with the glabrous (palmar) skin of either hand/foot either numerically or using a visual analogue scale.<br>* Other names: Heat Foil device;Device: functional magnetic resonance imaging for Brain Neuroimaging<br>* to evaluate baseline changes in regional cerebral blood flow to nociceptive thermal stimuli applied to the extremities of FM patients and healthy volunteers.<br>* Other names: fMRI;Device: fMRI for Spinal Cord Neuroimaging<br>* The subjects will be positioned supine and immobilized by means of a padded head support. The spinous process of the first thoracic vertebra (T1) will be aligned with the center of surface Neuro - coil. This coil will be employed for both transmission of radio-frequency (RF) pulses and detection of the magnetic resonance (MR) signal. A modified FLASH sequence will be employed to obtain Blood Oxygen Level Dependent (BOLD)-sensitive images of the spinal cord.<br>* Other names: functional magnetic resonance imaging;|
| Experimental: Fibromyalgia Only<br>The diagnosis of FM will require a history of chronic widespread pain as well as the presence of at least eleven out of eighteen paired tender points. Undergoing sensory testing, brain and spinal cord neuroimaging and Inventory assessments. | Device: A Peltier for Sensory testing<br>* Subjects will be trained to rate the magnitude of late sensations elicited following brief (700 msec) contact of a preheated thermode with the glabrous (palmar) skin of either hand/foot either numerically or using a visual analogue scale.<br>* Other names: Heat Foil device;Device: functional magnetic resonance imaging for Brain Neuroimaging<br>* to evaluate baseline changes in regional cerebral blood flow to nociceptive thermal stimuli applied to the extremities of FM patients and healthy volunteers.<br>* Other names: fMRI;Device: fMRI for Spinal Cord Neuroimaging<br>* The subjects will be positioned supine and immobilized by means of a padded head support. The spinous process of the first thoracic vertebra (T1) will be aligned with the center of surface Neuro - coil. This coil will be employed for both transmission of radio-frequency (RF) pulses and detection of the magnetic resonance (MR) signal. A modified FLASH sequence will be employed to obtain Blood Oxygen Level Dependent (BOLD)-sensitive images of the spinal cord.<br>* Other names: functional magnetic resonance imaging;|
| Experimental: Chronic fatigue and Fibromyalgia Syndrome<br>Diagnosis of ME/CFS will require a history of chronic fatigue persisting or relapsing for more than 6 months as well as the presence of at least four out of eight designated symptoms. Undergoing sensory testing, brain and spinal cord neuroimaging and Inventory assessments. | Device: A Peltier for Sensory testing<br>* Subjects will be trained to rate the magnitude of late sensations elicited following brief (700 msec) contact of a preheated thermode with the glabrous (palmar) skin of either hand/foot either numerically or using a visual analogue scale.<br>* Other names: Heat Foil device;Device: functional magnetic resonance imaging for Brain Neuroimaging<br>* to evaluate baseline changes in regional cerebral blood flow to nociceptive thermal stimuli applied to the extremities of FM patients and healthy volunteers.<br>* Other names: fMRI;Device: fMRI for Spinal Cord Neuroimaging<br>* The subjects will be positioned supine and immobilized by means of a padded head support. The spinous process of the first thoracic vertebra (T1) will be aligned with the center of surface Neuro - coil. This coil will be employed for both transmission of radio-frequency (RF) pulses and detection of the magnetic resonance (MR) signal. A modified FLASH sequence will be employed to obtain Blood Oxygen Level Dependent (BOLD)-sensitive images of the spinal cord.<br>* Other names: functional magnetic resonance imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in experimental pain from heat pulses to the upper extremities | Numerical ratings from 0 to 100 are tied to verbal descriptors in increments of 5, to standardize the scale, and ratings in increments of 5 are permitted. Ratings of 0 and 15 designate non-painful sensations of warmth (5 = threshold for warmth, 15 = suprathreshold warmth). A rating of 20 = threshold for heat pain, 30 = very weak pain, 40 = weak pain, 50 = moderate pain, 60 = slightly strong pain, 70 = strong pain, 80 = very strong pain, 90 = extreme strong pain, and 100 = the most intense pain imaginable | 3 intervals of 30 seconds each | 
| Change in experimental Pain from mechanical stimulation to the upper extremities and the shoulder | Numerical ratings from 0 to 100 are tied to verbal descriptors in increments of 5, to standardize the scale, and ratings in increments of 5 are permitted. Ratings of 0 and 15 designate non-painful sensations of warmth (5 = threshold for warmth, 15 = suprathreshold warmth). A rating of 20 = threshold for heat pain, 30 = very weak pain, 40 = weak pain, 50 = moderate pain, 60 = slightly strong pain, 70 = strong pain, 80 = very strong pain, 90 = extreme strong pain, and 100 = the most intense pain imaginable | 3 intervals of 30 seconds each | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fatigue Ratings | Visual analogue scale ratings (0-10) on a 15 cm mechanical scale. The scale is limited on the left by no fatigue at all and on the right by most intense fatigue imaginable | baseline and up to 3 hours. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Fatigue