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

NCT ID: NCT03075254

Last Updated: 2025-01-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 197 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-03-15
• Study Completion Date: 2024-10-29

Brief Summary

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

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.

Conditions

Chronic Fatigue Syndrome; Fibromyalgia

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy Control

normal volunteers (HC) Undergoing sensory testing, brain and spinal cord neuroimaging and Inventory assessments.

A Peltier for Sensory testing

Intervention Type: DEVICE

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.

functional magnetic resonance imaging for Brain Neuroimaging

Intervention Type: DEVICE

to evaluate baseline changes in regional cerebral blood flow to nociceptive thermal stimuli applied to the extremities of FM patients and healthy volunteers.

fMRI for Spinal Cord Neuroimaging

Intervention Type: DEVICE

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.

Fibromyalgia Only

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.

A Peltier for Sensory testing

Intervention Type: DEVICE

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.

functional magnetic resonance imaging for Brain Neuroimaging

Intervention Type: DEVICE

to evaluate baseline changes in regional cerebral blood flow to nociceptive thermal stimuli applied to the extremities of FM patients and healthy volunteers.

fMRI for Spinal Cord Neuroimaging

Intervention Type: DEVICE

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.

Chronic fatigue and Fibromyalgia Syndrome

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.

A Peltier for Sensory testing

Intervention Type: DEVICE

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.

functional magnetic resonance imaging for Brain Neuroimaging

Intervention Type: DEVICE

to evaluate baseline changes in regional cerebral blood flow to nociceptive thermal stimuli applied to the extremities of FM patients and healthy volunteers.

fMRI for Spinal Cord Neuroimaging

Intervention Type: DEVICE

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.

Interventions

A Peltier for Sensory testing

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.

Intervention Type: DEVICE

functional magnetic resonance imaging for Brain Neuroimaging

to evaluate baseline changes in regional cerebral blood flow to nociceptive thermal stimuli applied to the extremities of FM patients and healthy volunteers.

Intervention Type: DEVICE

fMRI for Spinal Cord Neuroimaging

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.

Intervention Type: DEVICE

Other Intervention Names

Heat Foil device; fMRI; functional magnetic resonance imaging

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roland Staud, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

Other Identifiers

IRB201602417 -N-A

Identifier Type: -

Identifier Source: org_study_id