Harnessing Theta-Gamma Coupled Brainwave Using Ultrasound for Spinal Astrocyte Revitalization and Sustained Neuropathic Pain Relief

Harnessing Theta-Gamma Coupled Brainwave Using Ultrasound for Spinal Astrocyte Revitalization and Sustained Neuropathic Pain Relief | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Harnessing Theta-Gamma Coupled Brainwave Using Ultrasound for Spinal Astrocyte Revitalization and Sustained Neuropathic Pain Relief Joo Min Park, Tien Phan, Ho Jeong Kim, Keunhyung Lee, Dong-Wook Kang, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4775433/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Dec, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Ultrasound stimulation is a promising non-invasive method for pain treatment, but comprehending its long-lasting impact and mechanisms remains challenging. Here, we investigate the neuromodulation effects of patterned ultrasound, focusing on spinal astrocytes in a partial sciatic nerve crush injury (PCI) model. Low-intensity continuous theta burst ultrasound stimulation with gamma bursts (LI-cTBUS) provides significant pain relief during and after application. LI-cTBUS enhances extracellular BDNF uptake by spinal astrocytes, restoring balance in the spinal BDNF/TrkB/KCC2 pathway, and reduces reactive astrogliosis by activating the TRPA1 ion channel, suggesting its role in ultrasound-induced analgesia. PCI alters the spinal cord transcriptomics, but LI-cTBUS normalizes these changes by attenuating inflammatory pathways, downregulating BDNF/TrkB signaling, and regulating GABA neurotransmission. Overall, LI-cTBUS revitalizes reactive astrocytes, reducing astrogliosis and nociceptive responses, highlighting its efficacy in alleviating mechanical allodynia and providing sustained neuropathic pain relief, underscoring its therapeutic potential. Biological sciences/Neuroscience/Cellular neuroscience Biological sciences/Neuroscience/Diseases of the nervous system/Chronic pain Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementaryvideo.zip Walking gait FiguresNatureNeuroscience.pdf 5 main figures; 12 supplementary figures SupplementaryMaterialsPhanetal.pdf Supplementary data Cite Share Download PDF Status: Published Journal Publication published 06 Dec, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4775433","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":337211148,"identity":"1e241777-3e15-42ab-a91d-aa32f9767faa","order_by":0,"name":"Joo Min 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