Low-intensity transcranial focused ultrasound suppresses pain by modulating pain-processing brain circuits.

Autor:	Kim MG; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA., Yu K; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA., Yeh CY; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA., Fouda R; Department of Medicine, University of California, Irvine, Irvine, CA., Argueta D; Department of Medicine, University of California, Irvine, Irvine, CA., Kiven S; Department of Medicine, University of California, Irvine, Irvine, CA., Ni Y; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA., Niu X; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA., Chen Q; Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Kim K; Department of Medicine, University of Pittsburgh, Pittsburgh, PA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA., Gupta K; Department of Medicine, University of California, Irvine, Irvine, CA., He B; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA.; Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Sep 05; Vol. 144 (10), pp. 1101-1115.
DOI:	10.1182/blood.2023023718
Abstrakt:	Abstract: There is an urgent and unmet clinical need to develop nonpharmacological interventions for chronic pain management because of the critical side effects of opioids. Low-intensity transcranial focused ultrasound (tFUS) is an emerging noninvasive neuromodulation technology with high spatial specificity and deep brain penetration. Here, we developed a tightly focused 128-element ultrasound transducer to specifically target small mouse brains using dynamic focus steering. We demonstrate that tFUS stimulation at pain-processing brain circuits can significantly alter pain-associated behaviors in mouse models in vivo. Our findings indicate that a single-session focused ultrasound stimulation to the primary somatosensory cortex (S1) significantly attenuates heat pain sensitivity in wild-type mice and modulates heat and mechanical hyperalgesia in a humanized mouse model of chronic pain in sickle cell disease. Results further revealed a sustained behavioral change associated with heat hypersensitivity by targeting deeper cortical structures (eg, insula) and multisession focused ultrasound stimulation to S1 and insula. Analyses of brain electrical rhythms through electroencephalography demonstrated a significant change in noxious heat hypersensitivity-related and chronic hyperalgesia-associated neural signals after focused ultrasound treatment. Validation of efficacy was carried out through control experiments, tuning ultrasound parameters, adjusting interexperiment intervals, and investigating effects on age, sex, and genotype in a head-fixed awake model. Importantly, tFUS was found to be safe, causing no adverse effects on motor function or the brain's neuropathology. In conclusion, the validated proof-of-principle experimental evidence demonstrates the translational potential of novel focused ultrasound neuromodulation for next-generation pain treatment without adverse effects. (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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