NCT06472622 · National Institute of Neurological Disorders and Stroke (NINDS)
Functional Neuroimaging to Detect the Neural Signatures of the Unpleasantness of Pain and Effort
What this study is about
Background: The way the brain processes rewards and punishments may play a role in some disorders of the nervous system. People with chronic overlapping pain conditions (such as myalgic encephalomyelitis/chronic fatigue syndrome \[ME/CFS\]) may have heightened responses to unpleasant, punishing sensations.
View original scientific description
Background: The way the brain processes rewards and punishments may play a role in some disorders of the nervous system. People with chronic overlapping pain conditions (such as myalgic encephalomyelitis/chronic fatigue syndrome \[ME/CFS\]) may have heightened responses to unpleasant, punishing sensations. Some of these conditions may also cause heightened responses to effort; this is an unpleasant sensation felt during physical and mental exertion. Objective: To learn more about how the brain processes different unpleasant sensations. Eligibility: People aged 18 to 50 years with ME/CFS. Healthy volunteers are also needed. Design: Participants will have 3 visits in 1 to 5 weeks. Visit 1: Participants may have a neurologic exam. They will have a mock magnetic resonance imaging (MRI) scan. They will lie on a bed in a wooden tube while they practice 2 tasks: Thermal pain rating: A device that creates mild to moderate heat will be placed on one leg. Physical effort rating: Participants will squeeze a plastic bar with different levels of force. Visit 2: Participants will have a real MRI scan. They will lie on a table that slides into a large tube. Visit 3: Participants will have another MRI scan. They will repeat the thermal pain and physical effort tasks while in the scanner. Sensors will be placed on 1 arm to measure how the muscles function as they squeeze the bar. Their heart rate will be tested: They will hold their finger against a camera lens for 1 minute. They will do 2 other tasks: 1 requires repeatedly pressing a key on a keyboard, and the other requires squeezing a bar.
Interventions
DEVICE
Thermal Pain Stimulation
Thermal pain will be administered during fMRI neuroimaging via a thermal stimulation device (Medoc Ltd., Advanced Medical System, Israel; 510K: K052357; K041908; K922052) to examine brain activity corresponding to the experience of this stimulus. This device and associated system carries an FDA 510 (K) clearance.
DEVICE
Physical Effort Stimulation
Physical effort will be administered during fMRI neuroimaging via a hand dynamometer attachment for a physiological monitoring system (BIOPAC Systems, Inc., Goleta, CA, USA) to examine brain activity corresponding to the experience of this stimulus. This device has not received pre-marked approval or 510 (K) clearance by the FDA.
Primary outcome measures
Determine which regions of the SVN are specifically involved in the subjective experience of unpleasantness associated with sensations of pain.
Time frame: The measurement will be assessed concurrently with thermal pain stimulus administration during the fMRI procedure associated with one of the study visits, 1-31 days following the visit for the first session.
SVN regions in which activity is significantly associated with unpleasantness of pain.
Determine which regions of the SVN are specifically involved in the subjective experience of unpleasantness associated with sensations of physical effort.
Time frame: The measurement will be assessed concurrently with physical effort stimulus administration during the fMRI associated with one of the study visits, 1-31 days following the visit for the first session.
The SVN has been hypothesized to play a role in producing the unpleasantness of negative experiences including effort.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Healthy Controls: In order to be eligible to participate in this study as a healthy control, an individual must meet all the following criteria:
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, aged 18-50 (inclusive).
- Good general health as evidenced by medical history and/or physical examination. ME/CFS Patients: In order to be eligible to participate in this study as an ME/CFS patient, an individual must meet all the following criteria:
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, aged 18-50 (inclusive).
- Has a diagnosis of ME/CFS, meeting at least one of three ME/CFS criteria: the 1994 Fukuda Criteria, the 2003 Canadian Consensus Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, or the Institute of Medicine Diagnostic Criteria.
Exclusion criteria
- Healthy Controls:
- Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson s disease, Alzheimer s disease, schizophrenia, or major depressive disorder.
- Any other current major medical disorder, such as a kidney disease, liver disease, cardiovascular disease, chronic pain condition, or any other disorder which, in the opinion of the PI would make participation risky for the individual or negatively affect the individual s ability to cooperate with study procedures.
- Current use of medications acting primarily on the central nervous system, such as antidepressants, stimulants, etc.
- Use of opioid medications for more than two weeks within the last two years or any use in the last month.
- Current or history of substance use disorder, binge drinking, illegal drug use, or excessive tobacco use (defined as more than 10 cigarettes of nicotine per week).
- Any more than occasional use of cannabis, defined as a score \>1 (indicating use on more than one or two days in the last two weeks) on the marijuana use item of the DSM-5 Level 2-Substance Use-Adult questionnaire.
- Any use of other illicit drugs or misuse of prescription medications, defined as a score \>0 on any of the other items of the DSM-5 Level 2-Substance Use-Adult questionnaire.
- Condition or injury affecting grip.
- Condition or injury affecting extremities that would alter peripheral sensitivity to painful thermal stimuli or would otherwise cause such stimuli to be contraindicated.
- Contraindications to MRI, including ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body, implanted cardiac pacemaker, auto-defibrillator, or pump, non-removable body piercing, claustrophobia, inability to lie supine for 90 minutes, known pregnancy, or plans to become pregnant during the study.
- Members of the NINDS BNU and their family members.
- Non-English speakers will be excluded from the study as several study instruments do not have validated translations. ME/CFS Patients:
- Any current major neurological or psychiatric disorder, other than ME/CFS, such as (but not limited to) stroke, Parkinson s disease, Alzheimer s disease, schizophrenia, or major depressive disorder.
- Any other current major medical disorder, other than ME/CFS, such as a kidney disease, liver disease, cardiovascular disease, chronic pain condition, or any other disorder which, in the opinion of the PI would make participation risky for the individual or negatively affect the individual s ability to cooperate with study procedures.
- Current use of psychomotor stimulants, antipsychotics, or benzodiazepines.
- Use of opioid medications for more than two weeks within the last two years or any use in the last month.
- Current or history of substance use disorder, binge drinking, illegal drug use, or excessive tobacco use (defined as more than 10 cigarettes of nicotine per week).
- Any more than occasional use of cannabis, defined as a score \>1 (indicating use on more than one or two days in the last two weeks) on the marijuana use item of the DSM-5 Level 2-Substance Use-Adult questionnaire.
- Any use of other illicit drugs or misuse of prescription medications, defined as a score \>0 on any of the other items of the DSM-5 Level 2-Substance Use-Adult questionnaire.
- Condition or injury affecting grip.
- Condition or injury affecting extremities that would alter peripheral sensitivity to painful thermal stimuli or would otherwise cause such stimuli to be contraindicated.
- Contraindications to MRI, including ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body, implanted cardiac pacemaker, auto-defibrillator, or pump, non-removable body piercing, claustrophobia, inability to lie supine for 90 minutes, known pregnancy, or plans to become pregnant during the study.
- Members of the NINDS BNU and their family members.
- Non-English speakers will be excluded from the study as several study instruments do not have validated translations.
Where
- Bethesda, Maryland
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 13, 2026 · Source of record for eligibility and locations