A novel noninvasive technique using focused ultrasound to modulate deep brain regions involved in pain processing demonstrated significant reductions in chronic pain, according to findings from a small randomized controlled trial.
The study, published in PAIN, found that a single 40-minute session targeting the anterior cingulate cortex (ACC) led to rapid, clinically meaningful, and durable pain relief compared to sham stimulation. Researchers at the University of Utah conducted a double-blind, randomized, sham-controlled crossover trial involving 23 patients with various chronic pain conditions. Using a device that focuses low-intensity ultrasonic waves through the intact skull, they targeted eight subregions within the ACC, a deep brain structure implicated in the affective component of pain.
Key Findings
Active stimulation reduced pain by 60.0% immediately following intervention, compared to 14.4% for sham (P = .00013, z = 3.83, Wilcoxon signed-rank test).
At 24 hours post-treatment, 60% of participants reported clinically meaningful pain reduction (>33%) with active stimulation vs 15% with sham.
Pain relief persisted through 7 days of follow-up, with a 33.0% reduction for active stimulation vs 6.6% for sham at day 7.
PROMIS pain intensity scores decreased by 5.68 points with active stimulation vs 0.23 points with sham (P = .0014).
No serious adverse events were reported with active stimulation, with side effects being generally mild and resolving within 24 hours.
Study Details and Methods
The study population was 60% female, with a mean age of 46.6 years. Baseline Brief Pain Inventory (BPI) 24-Hour Average Pain scores were 5.35 for active and 5.21 for sham conditions. Participants had various chronic pain conditions, including fibromyalgia (n=10), myofascial pain syndrome (n=4), generalized pain syndrome (n=4), migraines (n=3), back pain (n=3), neuropathy (n=3), and arthritis (n=3).
The device used measured and compensated for ultrasound attenuation by the skull, allowing controlled delivery to deep brain targets. Ultrasound parameters included 1 MPa amplitude, 650 kHz frequency, with spatial peak pulse average intensity of 31.0 W/cm^2, mechanical index of 1.2, and thermal index of 0.64.
Participants underwent an initial magnetic resonance imaging (MRI) session for anatomical targeting, followed by a 40-minute treatment session outside the scanner. The protocol included two stimulation blocks:
- Sixteen 30-second sonications to eight ACC targets to identify most effective locations
- Twelve 3-minute sonications to the four most responsive targets.
Sham condition involved auditory masking without ultrasound delivery.
MRI acquisition used a Siemens VIDA 3T system. Functional MRI BOLD parameters included TR 2.0s, TE 33ms, flip angle 80°, 52 slices, 2.4mm thickness. MPRAGE anatomical scans used TR 2.4s, TE 2.26ms, flip angle 8°, 192 slices, 1.3mm thickness.
Functional MRI validation confirmed modulation of ACC activity in most subjects receiving active stimulation. Target engagement data showed significant effects in three of four participants for subgenual ACC, and three of five participants for dorsal ACC. Subgenual ACC stimulation consistently showed deactivation, while dorsal ACC showed mixed activation/deactivation patterns.
The primary outcome was change in Brief Pain Inventory 24-hour average pain score; secondary measures included PROMIS pain intensity, depression, and anxiety scores. The crossover design allowed comparison of active vs sham stimulation in the same individuals after a 1-week washout period.
Results were analyzed using repeated measures ANOVA (F_7 = 3.21, P = 0.0086, Greenhouse-Geisser adjusted) and Wilcoxon signed-rank tests for non-normally distributed data.
Additional Findings
At 24 hours post-treatment, 55% of participants had >50% pain reduction with active stimulation vs 10% with sham. At 7 days post-treatment, 30% had >50% pain reduction with active stimulation vs 10% with sham.
PROMIS depression scores decreased by 2.27 points for active stimulation vs 0.23 for sham (P = 0.14), and PROMIS anxiety scores decreased by 2.87 points for active stimulation vs 0.65 for sham (P = 0.20).
Safety data showed no significant differences in side effects between active and sham conditions. The most common side effects were headache (20% active, 25% sham), dry mouth (5% active, 0% sham), and dizziness (5% active, 0% sham).
The researchers noted several limitations of the study, including small sample size, heterogeneous pain conditions, and relatively short follow-up period. They emphasized the need for larger studies to determine optimal patient selection, treatment protocols, and long-term efficacy.
One author is an inventor on a patent related to the device function. The other authors have no conflict of interests to declare.