Treating Pain with Focused Ultrasound: Two Neuromodulation Clinical Trials

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Key Points

  • One trial targeted the subregions of the insula for pain processing and heart rate variability. 
  • The other trial targeted the dorsal anterior cingulate for acute pain perception and autonomic responses.

Researchers from the Fralin Biomedical Research Institute at VTC and the School of Neuroscience at Virginia Tech recently published results from two clinical trials investigating the use of low-intensity focused ultrasound (LIFU) neuromodulation for the treatment of pain. 

Both projects were led by Wynn Legon, PhD, an assistant professor at both the Fralin Biomedical Research Institute and Virginia Tech’s School of Neuroscience.  

“Increasing the body’s ability to deal with and respond to pain may be an important means of reducing disease burden,” said Dr. Legon in the Virginia Tech press release. 

The studies used the BrainSight neuronavigation system to determine the placement of the LIFU transducer on the scalp and two different preclinical transducers (with unique focal depths) to apply the LIFU. 

Noninvasive Neuromodulation of Subregions of the Human Insula Differentially Affect Pain Processing and Heart-Rate Variability: A Within-Subjects Pseudo-Randomized Trial 

  • In this study, the team sought to determine whether focused ultrasound could noninvasively reach and then neuromodulate two of the insula subregions of the brain (anterior and posterior). These regions are responsible for sensing pain, body awareness, and autonomic heart rate variability, among others. 
  • After enrolling 23 healthy volunteers (7 males and 16 females with an average age of 27 ± 5.5 years old; range 19–45 years) in a pseudo-randomized trial design, the team measured responses to pain (heat that was briefly applied to the back of their hand). Data were collected on pain rating, heart rate, brain activity, and electrodermal activity. Through the use of many validated questionnaires, additional data were collected regarding depression, anxiety, sleep, general health, and more. 
  • During the trial, the researchers randomized participants to receive LIFU to the anterior insula, LIFU to the posterior insula, or a sham treatment during three different sessions. They then collected the same data after the treatment that they had collected before treatment. Pain rating was the primary outcome measure. 
  • The group determined that LIFU reduced pain ratings when applied to either the anterior or posterior area of the insula; however, the neuromodulation to each area produced slightly different effects on brain activity, and heart rate variability was affected only when the LIFU was applied to the anterior part of the insula. 
  • The Focused Ultrasound Foundation’s advocacy efforts helped provide State of Virginia co-funding for this work. 
  • See PAIN (Open Source). 
  • See Virginia Tech’s Press Release on this study. 

Low-Intensity Focused Ultrasound to the Human Dorsal Anterior Cingulate Attenuates Acute Pain Perception and Autonomic Responses 

  • In this study, the team tested whether LIFU could noninvasively reach and then neuromodulate the dorsal anterior cingulate cortex (dACC) of the brain. This region is responsible for pain processing, autonomic control, cognitive/executive function, and learning. Pain challenges the autonomic nervous system, making the dACC an interesting target because it integrates cognitive processes with pain and autonomic responses. 
  • Researchers measured responses to pain (heat briefly applied to the back of the participant’s hand) in 16 healthy volunteers (6 males and 10 females with an average age of 28 ± 5.46 years old). Subjective pain and heart rate variability were the primary outcome measures. 
  • Data were collected before, during, and after the LIFU during one session and a sham treatment during another session, including a baseline report of symptoms questionnaire, electroencephalogram (EEG), electrocardiogram (ECG) and electrodermal response (EDR). 
  • LIFU noninvasively reduced pain by roughly 1 point on a 10 point scale and altered autonomic responses to the painful stimuli. 
  • See the Journal of Neuroscience
  • See Virginia Tech’s Press Release on this study. 

Both clinical trials showed that LIFU could be an effective method for noninvasive neuromodulation of pain, and that it works differently in specific regions of the brain. 

Media coverage of these studies included Science Daily, The Science Times, Trial Bulletin, Brain Tomorrow, Health Imaging, Medriva, Health Management, Pain Medicine News, and more.