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Blood, Jul 08 2024, blood.2023023718 | https://doi.org/10.1182/blood.2023023718
Low-intensity transcranial focused ultrasound suppresses pain by modulating pain processing brain circuits
Min Gon Kim1,†, Kai Yu1,†, Chih-Yu Yeh1, Raghda Fouda2, Donovan Argueta2, Stacy Kiven2, Yunruo Ni1, Xiaodan Niu1, Qiyang Chen3, Kang Kim3,4, Kalpna Gupta2, and Bin He1,5*
1Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213
2Department of Medicine, University of California at Irvine, Irvine, CA 92697
3Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261
4Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261
5Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA 15213
†These authors contributed equally to this work.
*Corresponding Author: Bin He, Ph.D.
Abstract
There is an urgent and unmet clinical need to develop non-pharmacological interventions for chronic pain management due to the critical side effects of opioids. Low-intensity transcranial focused ultrasound is an emerging non-invasive 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, employing dynamic focus steering. We demonstrate that transcranial focused ultrasound 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 (e.g., insula) and multi-session focused ultrasound stimulation to S1 and insula. Analyses of brain electrical rhythms through electroencephalography demonstrated a significant change in noxious heat hypersensitive- and chronic hyperalgesia-associated neural signals following focused ultrasound treatment. Validation of efficacy was carried out through control experiments, tuning ultrasound parameters, adjusting inter-experiment intervals, and investigating effects on age, gender, genotype, and in a head-fixed awake model. Importantly, transcranial focused ultrasound was found to be safe, causing no adverse effects on motor function and 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.
논문정보
- Research article
- 2024년 07월 (BRIC 등록일 2024-07-10)
- 국외 연구진
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