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.
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.
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
Crossover
low intensity focused ultrasound (LIFU)
DeviceLow-intensity focused ultrasound (LIFU) provides an energy source with millimeter resolution that can be focused anywhere in the brain safely and effectively for non-invasive and transient neuromodulation. LIFU is an important advance and of great significance for brain-mapping efforts, diagnostics, and therapies in neuroscience and particularly promising for addiction therapy as it provides unprecedented non-surgical access to the brain regardless of depth. Much lower intensities of focused ultrasound (LIFU) are used so that tissue damage does not occur, but neural activity can be modulated. LIFU utilizes acoustic energy at much lower levels to affect tissue by mechanical effects.
Measures of Central Sensitization - Thermal Pain Threshold
For the first measure, the probe is placed on the skin on the ventral aspect of the forearm on the nondominant arm. The temperature is set at 32°C and the temperature is increased at a rate of 1°C/s to a maximum of 52°C. Participants will be asked to press a button when the heat reaches a painful level. The outcome is the temperature at this level. Heat PT are averaged over three trials each separated by 40 seconds. Thermal PT will be performed prior to and after LIFU. On each trial, the thermode is moved to a different site on the forearm to avoid sensitization and response suppression of cutaneous heat receptors.
Measures of Central Sensitization - Temporal Summation of Pain
The second measure refers to the perception of increasing pain in response to repeated same noxious stimuli delivered at a frequency of \> 0.33 Hz. Temporal summation of pain serves as a proxy measure of pain facilitation and CS. Individuals with enhanced temporal summation of pain have facilitated ascending nociceptive processing and reduced pain-modulatory capacities. Following the temporal summation of pain paradigm, three stimulus trains of trapezoid heat pulses of 1.5 s duration will be delivered to the dorsum of the dominant hand at an inter-pulse interval of 2.5 seconds at individual subject heat pain of 6/10 on numeric pain rating scale. A total of 5 stimuli will be delivered per train. Participants will be required to rate each stimulus (0-10). The Δ scores from 5th to 1st stimulus of each train will be averaged.
Measures of Central Sensitization - Conditioned Modulation of Pain
A type of counter-irritation paradigm that can be used as a proxy measure for descending anti-nociceptive or pain modulation activity. CPM involves presentation of a conditioning pain stimulus to a remote area of the body while a nociceptive (test) stimulus (TS) is applied to the contralateral (heterotopic) area. We will employ conditioned modulation of pain according to using a sequential conditioning-test stimulus protocol as recommended by. The test stimulus consists of a two-minute thermal stimulus applied with the thermode at a rating of 5/10 on the numeric pain rating scale. Participants will rate their perceived pain (0-10, numeric pain rating scale) every 15 seconds. This will be performed pre/post the conditioning stimulus. The conditioning stimulus will be a cold pressor test.. The non-dominant arm will be immersed in a cold-water bath (12°C) for two minutes. This method recruits inhibitory conditioned modulation of pain because it is a strong nociceptive stimulation.
Neurologic Pain Signature
A secondary outcome is the pain intensity and magnitude of the NPS in response to evoked thermal pain using task-based functional magnetic resonance imaging.
Tonic Pain Signature
A secondary outcome is the pain intensity and magnitude of Tonic Pain Signature in response to tonic pain using resting-state functional magnetic resonance imaging.
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