NCT05285683 · University of Rochester
The Role of Brain Dopamine in Chronic Pain
What this study is about
Chronic pain is associated with plasticity in the brain limbic system composed mainly of the amygdala, hippocampus, ventral striatum, and cingulate cortex (ACC) /medial prefrontal cortex (mPFC). These brain areas, especially the ventral striatum, receive dopaminergic input from the ventral-tegmental area (VTA).
View original scientific description
Chronic pain is associated with plasticity in the brain limbic system composed mainly of the amygdala, hippocampus, ventral striatum, and cingulate cortex (ACC) /medial prefrontal cortex (mPFC). These brain areas, especially the ventral striatum, receive dopaminergic input from the ventral-tegmental area (VTA). Although there is a significant literature now showing that limbic brain tracks chronic pain intensity and predicts the risk of transition from sub-acute to chronic pain, the role of dopaminergic input to the limbic brain and the change thereof which occurs in chronic pain, is still not clear. Given the role of dopamine in motivational control and the loss of motivation associated with chronic pain understanding how dopaminergic transmission is altered in the limbic brain of chronic pain patients is critical to the understanding of the pathophysiology of chronic pain. Therefore, the overall aim of this project is to use brain imaging to study how dopaminergic transmission through the oral administration of pro-dopaminergic medications carbidopa/levodopa (CD/LD) and methylphenidate will modulate the brain signature of chronic pain. Chronic pain subjects will be scanned at baseline (no drug administration) and three times after treatment with the two drugs or placebo. The protocol will follow a randomized double-blind approach.
Interventions
DRUG
Methylphenidate
0.5 mg/kg
DRUG
carbidopa-levodopa
25 mg/100 mg
DRUG
Placebo
oral pill
Primary outcome measures
mean change in amygdala volume
Time frame: baseline to 3 hours
Amygdala volume will be measured using T1w MPRAGE structural images. The mean change in amygdala volume will be the volume of amygdala before administering the drug or placebo minus the volume of amygdala after administering the drug or placebo.
mean change in hippocampus volume
Time frame: baseline to 3 hours
Hippocampus volume will be measured using T1w MPRAGE structural images. The mean change in hippocampus volume will be the volume of hippocampus before administering the drug or placebo minus the volume of hippocampus after administering the drug or placebo.
mean change in thalamus volume
Time frame: baseline to 3 hours
Thalamus volume will be measured using T1w MPRAGE structural images. The mean change in thalamus volume will be the volume of thalamus before administering the drug or placebo minus the volume of thalamus after administering the drug or placebo.
mean change in Nucleus accumbens volume
Time frame: baseline to 3 hours
Nucleus accumbens volume will be measured using T1w MPRAGE structural images. The mean change in Nucleus accumbens volume will be the volume of Nucleus accumbens before administering the drug or placebo minus the volume of Nucleus accumbens after administering the drug or placebo.
mean change in amygdala activity
Time frame: baseline to 3 hours
Amygdala activity will be determined using Blood Oxygen Level Dependent (BOLD) fMRI sequences. The mean change in amygdala activity will be the activity of amygdala before administering the drug or placebo minus the activity of amygdala after administering the drug or placebo.
mean change in hippocampus activity
Time frame: baseline to 3 hours
Hippocampus activity will be determined using Blood Oxygen Level Dependent (BOLD) fMRI sequences. The mean change in hippocampus activity will be the activity of hippocampus before administering the drug or placebo minus the activity of hippocampus after administering the drug or placebo.
mean change in thalamus activity
Time frame: baseline to 3 hours
Thalamus activity will be determined using Blood Oxygen Level Dependent (BOLD) fMRI sequences. The mean change in thalamus activity will be the activity of thalamus before administering the drug or placebo minus the activity of thalamus after administering the drug or placebo.
mean change in Nucleus Accumbens activity
Time frame: baseline to 3 hours
Nucleus Accumbens activity will be determined using Blood Oxygen Level Dependent (BOLD) fMRI sequences. The mean change in Nucleus Accumbens activity will be the activity of Nucleus Accumbens before administering the drug or placebo minus the activity of Nucleus Accumbens after administering the drug or placebo.
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
- The following inclusion criteria must be met for all subjects to be considered eligible to participate:
- 18 years old or older
- Equal numbers of men and women, as well as racial and ethnic makeup representative of surrounding area
- Able to speak, read, and understand English
- In generally stable health
- Sign informed consent document The following inclusion criteria must be met for chronic pain patients to be considered eligible to participate:
- Patients must report chronic pain for more than 1 year.
- The reported pain should be rated at ≥ 40/100
Exclusion criteria
- General exclusion criteria for all subjects include:
- Significant other medical disease, such as unstable diabetes mellitus, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy
- History of traumatic brain injury (TBI)
- Current misuse/dependence on substance(s), including alcohol, at the time of study enrollment
- Major psychiatric disorder during the past 6 months
- Significantly abnormal laboratory values, which include, but are not limited to, the following:
- White blood cell (WBC) \< 1.5 or \>15.0 x 10\^3/μL
- Hemoglobin (Hgb) \< 8 gm/dL
- Hematocrit (Hct) \< 24% or \> 50%
- Platelets (Plts) \<50 or \> 1000 x10\^3
- Creatine \> 2 mg/dL
- Glucose \> 125 mg/dL
- Aspartate aminotransferase (AST) \> 250 U/L
- Alanine Transaminase (ALT) \> 250 U/L
- Bilirubin \> 3 mg/dL
- Intra-axial implants (e.g. - spinal cord stimulators or pumps)
- Inability to adequately perform the finger-span visual tracking task (training for rotating pain perception, see Brain Imaging Details).
- All MRI exclusionary criteria: any metallic implants, brain or skull abnormalities, tattoos on large body parts, pregnancy, and claustrophobia.
- In the judgement of the investigator, unable or unwilling to follow the protocol and instructions.
- Gambling addiction self-reported during screening process (ensure computer-based games do not cause psychological or emotional problems)
- Chronic pain patients with past history of allergic reactions to methylphenidate or levodopa/carbidopa. For healthy control subjects, current complaint(s) of pain, or a history of pain lasting \>4 weeks in the last year, will be excluded from participating. In addition, exclusion criteria for chronic pain subjects also includes:
- Pain that is associated with any systemic signs or symptoms (e.g. - fever, chills)
- Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, fibromyalgia, history of tumor(s) in the back.
- Involvement in litigation regarding their pain, or having a disability claim, or receiving workman's compensation, or seeking either because of their pain.
- Treated with methadone for opioid use disorder (i.e. - not just for pain)
Where
- Rochester, New York
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 15, 2026 · Source of record for eligibility and locations