The Role of Brain Dopamine in Chronic Pain

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.

Conditions

Chronic Pain

Talk to us

Study Overview

On this page

Study Details

Study overview

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.

The Role of Dopamine in the Central Neural Signature of Chronic Pain

The Role of Brain Dopamine in Chronic Pain

Condition
Chronic Pain
Intervention / Treatment

-

Contacts and Locations

Rochester

University of Rochester Medical Center, Rochester, New York, United States, 14642

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. 18 years old or older
  • 2. Equal numbers of men and women, as well as racial and ethnic makeup representative of surrounding area
  • 3. Able to speak, read, and understand English
  • 4. In generally stable health
  • 5. Sign informed consent document
  • 1. Patients must report chronic pain for more than 1 year.
  • 2. The reported pain should be rated at ≥ 40/100
  • 1. Significant other medical disease, such as unstable diabetes mellitus, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy
  • 2. History of traumatic brain injury (TBI)
  • 3. Current misuse/dependence on substance(s), including alcohol, at the time of study enrollment
  • 4. Major psychiatric disorder during the past 6 months
  • 5. Significantly abnormal laboratory values, which include, but are not limited to, the following:
  • 1. White blood cell (WBC) \< 1.5 or \>15.0 x 10\^3/μL
  • 2. Hemoglobin (Hgb) \< 8 gm/dL
  • 3. Hematocrit (Hct) \< 24% or \> 50%
  • 4. Platelets (Plts) \<50 or \> 1000 x10\^3
  • 5. Creatine \> 2 mg/dL
  • 6. Glucose \> 125 mg/dL
  • 7. Aspartate aminotransferase (AST) \> 250 U/L
  • 8. Alanine Transaminase (ALT) \> 250 U/L
  • 9. Bilirubin \> 3 mg/dL
  • 6. Intra-axial implants (e.g. - spinal cord stimulators or pumps)
  • 7. Inability to adequately perform the finger-span visual tracking task (training for rotating pain perception, see Brain Imaging Details).
  • 8. All MRI exclusionary criteria: any metallic implants, brain or skull abnormalities, tattoos on large body parts, pregnancy, and claustrophobia.
  • 9. In the judgement of the investigator, unable or unwilling to follow the protocol and instructions.
  • 10. Gambling addiction self-reported during screening process (ensure computer-based games do not cause psychological or emotional problems)
  • 11. Chronic pain patients with past history of allergic reactions to methylphenidate or levodopa/carbidopa.
  • 1. Pain that is associated with any systemic signs or symptoms (e.g. - fever, chills)
  • 2. Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, fibromyalgia, history of tumor(s) in the back.
  • 3. Involvement in litigation regarding their pain, or having a disability claim, or receiving workman's compensation, or seeking either because of their pain.
  • 4. Treated with methadone for opioid use disorder (i.e. - not just for pain)

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of Rochester,

Study Record Dates

2026-01-22