This research project is examining the effects of noninvasive brain stimulation on chronic pain. We believe this study will help us to better understand possible treatments for chronic pain patients. Subjects will undergo functional magnetic resonance imaging (fMRI) and a computed tomography (CT) scan, which is a way to take pictures of the brain and skull. Subjects will receive noninvasive brain stimulation using low-intensity focused ultrasound (LIFU) sound waves, to temporarily change brain activity. Subjects will undergo pain testing using a small device that will increase the temperature of their skin and will rate this pain. Brain signals (EEG), heart rate and rhythm, blood pressure, respiration rate, and skin moisture will be monitored. Subjects will complete behavioral questionnaires. Each study session is expected to take 1.5-3 hours. Total participation takes 10 weeks.

This is a 2-arm, sham-controlled, cross-over design. This study is collected over 5-7 study visits.

Initial Imaging (1): MRI and CT scans, Questionnaires, and QST Testing.

Intervention (2): Sham or verum LIFU application every 10 minutes, totaling in 8 applications. Between LIFU or Sham application quantitative sensory testing (QST) will be performed. Physiological data collection such as EEG, EDA, BP, ECG, and Respiration will be collected throughout the study visit.

Follow-Up Imaging (2-4): Following intervention sessions participants will receive a resting-state MRI. This can occur throughout the 4-weeks following an intervention visit. Participants will be scanned at least once after each intervention session.

Follow-Up Virtual Questionnaires: Following intervention sessions participants will receive a link (or a phone call if preferred) to periodically rate their pain and report on various lifestyle impacts of their chronic pain. Participants will complete these questionnaires at least twice per week in the 2 weeks following an intervention visit. These questionnaires will take less than 30 minutes.

After completing the intervention and minimum 4-week washout period, the participant will return for a second intervention visit and 3 week follow-up period.

Inclusion Criteria:

• Patients with a chronic pain diagnosis. Pain must be moderate-to-severe and present for at least 3 months prior to research participation. Patients of all ethnicities, who understand and speak English.

Exclusion Criteria:

• Claustrophobia (scanning environment may be uncomfortable).
• Contraindications to MRI: including pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants.
• Contraindications to CT: pregnancy
• Active medical disorder or treatment with potential CNS effects (e.g. Alzheimer's)
• History of neurologic disorder. (e.g. Parkinson's, Epilepsy, or Essential Tremor)
• History of head injury resulting in loss of consciousness for >10 minutes.
• History of alcohol or drug dependence (through self-report).