In this study, the research team will use low-intensity focused ultrasound (LIFU) to temporarily change brain activity in a brain region that is known to be involved in chronic pain. Through this, the research team hopes to learn about how the brain area works in response to pain. There are main questions this study aims to answer:

• The effect of LIFU to inhibit the posterior region of the insula (PI) compared to sham stimulation in individuals with chronic back pain (CBP) and widespread pain symptoms.
• The effect of LIFU to PI compared to sham stimulation to reduce pain intensity and magnitude of the Neurologic Pain Signature (NPS) in response to evoked thermal pain.
• The effect of LIFU to PI compared to sham stimulation to reduce pain intensity and magnitude of Tonic Pain Signature in response to tonic pain.

Chronic pain is a major public health problem. An estimated 100 million Americans have experienced chronic pain producing significant economic and social burden. The estimated annual cost of chronic pain is as high as $635 billion. Pharmacological treatments frequently require the use of opioids resulting in a major epidemic of abuse in the United States. New, non-addicting treatments for pain are critically needed. Neuromodulation with low-intensity focused ultrasound (LIFU) could represent a non-pharmacological treatment for chronic pain. The millimeter spatial specificity of LIFU makes it a powerful alternative to both invasive neurosurgical procedures and other noninvasive brain stimulation techniques. One promising target to treat chronic pain is the insular cortex. The insula as a key brain area involved in both sensory and affective components of chronic pain, including central sensitization processes which occur with pain chronicity. The insula is inaccessible using conventional noninvasive neuromodulatory techniques like transcranial magnetic stimulation. In contrast, LIFU can be focused deeply and provides the spatial resolution to resolve individual sub-regions of the insula. This is relevant to pain as the posterior subregion of the insula (PI) receives nociceptive input from spinothalamic tracts, relays it to the anterior insula which integrates expectation, awareness, and emotion to form the overall experience of pain. Therefore, using LIFU can address a gap in knowledge regarding the causal role of insular subregions in modulating pain response and CS processes. The preliminary data indicate that LIFU to PI reduces laboratory measures of central sensitization and evoked pain in healthy controls but there was no such effect of LIFU to anterior insula. Building on these results, the overall objective of this proposal is to examine the effect of LIFU to PI on the central sensitization processes that are a key feature of chronic pain syndromes and on neural response to evoked and tonic pain/pain intensity. The investigators will employ well validated laboratory measures of central sensitization and multivariate measures of neural response to evoked (Neurologic Pain Signature, NPS) and tonic (Tonic Pain Signature) pain. The chronic pain condition that the investigators will focus on in this study will be chronic back pain (CBP) with widespread pain widespread pain as the back is the most common site of chronic pain, is significantly more likely to be severe in the veteran population, and it commonly occurs with features of central sensitization. Eligible participants will have CBP with symptoms of widespread pain.

Inclusion Criteria:

• Veterans aged 21 to 75 with Chronic Back Pain (CBP).
• CBP duration daily for last 3 months or half of days for last 6 months
• Endorse pain rating of 4/10 BPI-SF
• Evidence of widespread pain symptoms as determined by report of CBP and pain in a contralateral limb (pain in the upper, lower, left or right side of the body) in fewer than 11 sites. Upper body sites include hand, wrist, elbow or shoulder. Lower sites include hip, knee, ankle or foot.

Exclusion Criteria:

• Surgery recommended as primary treatment intervention for CBP
• Current diagnosis of fibromyalgia
• Current substance use disorder other than nicotine.
• Psychiatric disorder and not on a stable pharmacologic regimen for ≥ 4 weeks prior to screening
• Opiate use daily
• Currently pregnant or breast feeding.
• Unable to understand the consent form.
• History of head injury with loss of consciousness for more than 5 minutes, seizures, history of stroke, brain surgery, brain tumor, multiple sclerosis.
• History of metastatic cancer, rheumatoid arthritis, polymyalgia rheumatica, scleroderma, lupus, or polymyositis
• Unintended weight loss of 20 pounds or more in the last year
• Cauda equina syndrome
• Ferromagnetic implants or other contraindications for MRI
• Uncompensated congestive heart failure, unstable angina, poorly controlled arrhythmia, active systemic infection end stage renal disease.

behavioral and imaging data

data will be available after analysis of primary and secondary outcomes are completed

The Sham condition will be conducted using an interface which does not allow ultrasound energy to pass from the transducer to the target. The administration of LIFU/sham will be conducted in a double-blind fashion.