PROACT

This mechanistic clinical trial proposes to test whether a five-day course of mindfulness meditation training (MMT) and tDCS, and their combination, can enhance pain modulatory balance and pain-related brain function, reduce clinical pain, among African Americans and non-Hispanic whites with knee osteoarthritis (OA). This approach will provide evidence that targeting stress and pain-related brain function will reduce OA-related pain and ethnic group differences therein.

Inclusion Criteria:

• Unilateral or bilateral symptomatic knee OA based on American College of Rheumatology Clinical criteria

• Participant reports primary ethnic/race group as either African American or non-Hispanic white

Exclusion Criteria:

• Actively symptomatic systemic rheumatic disease/condition (e.g. rheumatoid arthritis, systemic lupus erythematosus), or fibromyalgia that results in pain outside the knee that is equal to or worse than the participant's knee pain.

• A history of clinically significant surgery to the index knee.

• Daily use of opioids. We will exclude patients using opioids daily as both continued use and temporary withdrawal from these medications this could affect pain perception and response to interventions. Other medications being used will be recorded and controlled in statistical analyses as needed.

• Use of some centrally acting sodium channel blockers, calcium channel blockers and NMDA receptor antagonists, because some of these medications can block tDCS effects. Other medications can potentially influence response to tDCS (e.g. SSRIs, beta-blockers); therefore, consistent with recent recommendations (2), we will assess use of these medications and include them as covariates in our statistical models.

• Uncontrolled hypertension (i.e. SBP/DBP of > 150/95) or unstable or activity limiting cardiovascular or peripheral arterial disease. These exclusions are in place primarily for safety reasons, because the cold pressor task represents a cardiovascular challenge. However, uncontrolled hypertension can also affect pain perception, which is another reason for excluding these individuals.

• Neurological disease (e.g. Parkinson's, multiple sclerosis, epilepsy) or evidence of previous brain injury, including stroke and traumatic brain injury.

• Serious psychiatric disorder requiring hospitalization within the past 12 months or characterized by active suicidal ideation.

• Current substance use disorder or history of hospitalization for treatment of substance use disorder.

• Diminished cognitive function that would interfere with understanding of study procedures.