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Low-intensity focused ultrasound to the posterior insula reduces temporal summation of pain.

Authors: In A, Strohman A, Payne B, Legon W

The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization. Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective Determine whether low-intensity focused ultrasound targeted to the anterior insula, posterior insula, or dorsal anterior cingulate cortex modulates conditioned pain modulation and temporal summation of pain.
Animal model / Human subject Human (Homo sapiens); strain: N/A; age: 25.7 +- 3.4 years; sex: not reported; N=16 volunteers
Disease model Healthy
MRI or image guidance method MRI, CT, neuronavigation (BrainSight, Rogue Research, Montreal, QUE, CAN)
Targeted brain region(s) Anterior Insula (Ai), Posterior Insula (Pi), Dorsal Anterior Cingulate Cortex (Dacc)
Target coordinates dACC: MNI [0, 18, 30]

Outcomes and Safety

Summary of Outcomes LIFU to the posterior insula reduced temporal summation of pain vs sham, while anterior insula and dACC stimulation showed no effects.
Safety-related matter No serious adverse events were reported; the most common symptom was sleepiness and anxiousness was reported less frequently after interventions. Thermal simulations showed minimal heating (peak brain temperature rise ≈0.32 °C) and estimated intracranial pressures were reported but were not associated with adverse effects.

Brain Region

Ultrasound Parameters

Ultrasound instrument Single-element 500 kHz transducer Sonic Concepts H-281 (45.0 mm diameter, 38.0 mm focal lengteh) for insula; Single-element 500 kHz transducer Sonic Concepts H-104 (64.0 mm diameter, 52.0 mm focal length) for dACC
FUS Frequency 500 kHz
FUS Intensity Insula: Isppa 4.2 W/cm2, Ispta 1.5 W/cm2; dACC: Isppa 4.5 W/cm2, Ispta 1.62 W/cm2
FUS Pressure Insula: 380 kPa; dACC: 400 kPa
FUS Mode pulsed
Pulse duration 1 s
Duration of a single FUS session 10 minutes
Focal Characteristics Insula: Focal depth: 38 mm; Focal length: 38 mm; Aperture size: 45 mm; dACC: Focal depth: 52 mm; Focal length: 52 mm; Aperture size: 64 mm
Treatment frequency Single session

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