{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T18:15:14Z","timestamp":1775585714034,"version":"3.50.1"},"reference-count":69,"publisher":"AIP Publishing","issue":"1","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["EB029354"],"award-info":[{"award-number":["EB029354"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS131069"],"award-info":[{"award-number":["NS131069"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS124564"],"award-info":[{"award-number":["NS124564"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL147562"],"award-info":[{"award-number":["HL147562"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:p>Low-intensity transcranial focused ultrasound (tFUS) has recently been shown to noninvasively and non-pharmacologically modulate pain hypersensitivity with high spatial specificity and deep brain penetration. However, the lack of knowledge about its effectiveness for pain management in older subjects vulnerable to severe pain who are also at increased risk of cognitive impairment, presents significant challenges. Additionally, current opioid pain treatments require hospital visits, limiting unwanted serious side effects with multiple liabilities, and device-based pain treatments are typically administered at medical facilities with bulky and expensive equipment, limiting accessibility and thus highlighting the need for at-home non-pharmacological treatment options. Here, we present a more accessible, noninvasive tFUS pain treatment strategy for senior subjects. This approach involves simultaneously targeting multiple pain-processing circuits using a battery-powered, compact, and low-cost ultrasound analog front end (UAFE). We developed and evaluated the performance of the UAFE capable of generating sufficiently high-amplitude output with significantly lower noise levels compared to a commercial transmitter. Using a humanized sickle mouse model of chronic hyperalgesia, we found that tFUS stimulation targeting multiple pain-processing circuits effectively reduces heat hyperalgesia in aged female mice. In addition to its efficacy, our behavioral-based safety assessment revealed no adverse effects on motor functions. These results suggest that using a battery-powered, compact UAFE to simultaneously target multiple pain-processing circuits can effectively suppress heat pain-related behaviors in aged female sickle mice without negatively impacting motor coordination and balance. This highlights the potential for further development of fully home-based tFUS pain treatment for seniors.<\/jats:p>","DOI":"10.1063\/5.0236108","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T13:39:26Z","timestamp":1739972366000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Analgesic effect of simultaneously targeting multiple pain processing brain circuits in an aged humanized mouse model of chronic pain by transcranial focused ultrasound"],"prefix":"10.1063","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3414-1595","authenticated-orcid":false,"given":"Min Gon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Carnegie Mellon University 1 , Pittsburgh, Pennsylvania 15213,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5343-1181","authenticated-orcid":false,"given":"Chih-Yu","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Carnegie Mellon University 1 , Pittsburgh, Pennsylvania 15213,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4778-4389","authenticated-orcid":false,"given":"Kai","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Carnegie Mellon University 1 , Pittsburgh, Pennsylvania 15213,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7992-9995","authenticated-orcid":false,"given":"Zherui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Carnegie Mellon University 1 , Pittsburgh, Pennsylvania 15213,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9381-9979","authenticated-orcid":false,"given":"Kalpna","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California at Irvine 2 , Irvine, California 92697,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2944-8602","authenticated-orcid":false,"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Carnegie Mellon University 1 , Pittsburgh, Pennsylvania 15213,","place":["USA"]},{"name":"Neuroscience Institute, Carnegie Mellon University 3 , Pittsburgh, Pennsylvania 15213,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"317","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"issue":"9","key":"2025021913392163700_c1","doi-asserted-by":"publisher","first-page":"e3293","DOI":"10.7759\/cureus.3293","article-title":"Managing chronic pain in the elderly: An overview of the recent therapeutic advancements","volume":"10","year":"2018","journal-title":"Cureus"},{"issue":"8","key":"2025021913392163700_c2","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.3390\/biom11081256","article-title":"Chronic pain in the elderly: Mechanisms and distinctive features","volume":"11","year":"2021","journal-title":"Biomolecules"},{"key":"2025021913392163700_c3","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3389\/fnagi.2020.00116","article-title":"Age-related changes in pain perception are associated with altered functional connectivity during resting state","volume":"12","year":"2020","journal-title":"Front. Aging Neurosci."},{"issue":"2","key":"2025021913392163700_c4","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.jpain.2018.07.006","article-title":"Prevalence and profile of high impact chronic pain in the United States","volume":"20","year":"2019","journal-title":"J. Pain"},{"key":"2025021913392163700_c5","doi-asserted-by":"publisher","first-page":"h532","DOI":"10.1136\/bmj.h532","article-title":"Management of chronic pain in older adults","volume":"350","year":"2015","journal-title":"BMJ"},{"key":"2025021913392163700_c6","doi-asserted-by":"publisher","first-page":"3247","DOI":"10.2147\/IJGM.S419239","article-title":"Pharmacological methods of pain management: Narrative review of medication used","volume":"16","year":"2023","journal-title":"Int. J. Gen. Med."},{"key":"2025021913392163700_c7","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1046\/j.1532-5415.2001.49041.x","article-title":"Pain management in older adults: Prevention and treatment","volume":"49","year":"2001","journal-title":"J. Am. Geriatr. Soc."},{"issue":"10","key":"2025021913392163700_c8","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1001\/archinternmed.2011.152","article-title":"Geriatric drug evaluation: Where are we now and where should we be in the future?","volume":"171","year":"2011","journal-title":"Arch. Intern. Med."},{"key":"2025021913392163700_c9","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1001\/jama.2014.9405","article-title":"Management of persistent pain in the older patient: A clinical review","volume":"312","year":"2014","journal-title":"JAMA"},{"issue":"7","key":"2025021913392163700_c10","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/j.clinph.2006.03.025","article-title":"Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy","volume":"117","year":"2006","journal-title":"Clin. Neurophysiol."},{"issue":"2","key":"2025021913392163700_c11","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.clinph.2014.05.034","article-title":"The effects of transcranial direct current stimulation in patients with neuropathic pain from spinal cord injury","volume":"126","year":"2015","journal-title":"Clin. Neurophysiol."},{"issue":"3","key":"2025021913392163700_c12","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1109\/TBME.2013.2244890","article-title":"Neuromodulation for brain disorders: Challenges and opportunities","volume":"60","year":"2013","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"2025021913392163700_c13","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1146\/annurev.bioeng.9.061206.133100","article-title":"Noninvasive human brain stimulation","volume":"9","year":"2007","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"2025021913392163700_c14","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1016\/j.neuroimage.2011.02.058","article-title":"Focused ultrasound modulates region-specific brain activity","volume":"56","year":"2011","journal-title":"Neuroimage"},{"key":"2025021913392163700_c15","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/ima.20284","article-title":"Focused ultrasound modulates the level of cortical neurotransmitters: Potential as a new functional brain mapping technique","volume":"21","year":"2011","journal-title":"Int. J. Imaging Syst. Technol."},{"key":"2025021913392163700_c16","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1126\/science.127.3289.83","article-title":"Production of reversible changes in the central nervous system by ultrasound","volume":"127","year":"1958","journal-title":"Science"},{"key":"2025021913392163700_c17","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1121\/1.381829","article-title":"Auditory responses in cats produced by pulsed ultrasound","volume":"63","year":"1978","journal-title":"J. Acoust. Soc. Am."},{"issue":"1","key":"2025021913392163700_c18","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.brs.2019.09.011","article-title":"Transcranial focused ultrasound pulsation suppresses pentylenetetrazol induced epilepsy in vivo","volume":"13","year":"2020","journal-title":"Brain Stimul."},{"issue":"24","key":"2025021913392163700_c19","doi-asserted-by":"publisher","first-page":"01662","DOI":"10.1016\/j.biopsych.2024.09.029","article-title":"Noninvasive modulation of subcallosal cingulate and depression with focused ultrasonic waves","volume":"3223","year":"2024","journal-title":"Biol. Psychiatry"},{"key":"2025021913392163700_c20","doi-asserted-by":"publisher","first-page":"016033","DOI":"10.1088\/1741-2552\/ad27ef","article-title":"Noninvasive modulation of essential tremor with focused ultrasonic waves","volume":"21","year":"2024","journal-title":"J. Neural Eng."},{"issue":"6","key":"2025021913392163700_c21","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1016\/j.brs.2020.10.007","article-title":"Sonication of the anterior thalamus with MRI-guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study","volume":"13","year":"2020","journal-title":"Brain Stimul."},{"issue":"8","key":"2025021913392163700_c22","doi-asserted-by":"publisher","first-page":"e1011232023","DOI":"10.1523\/JNEUROSCI.1011-23.2023","article-title":"Low-Intensity focused ultrasound to the human dorsal anterior cingulate attenuates acute pain perception and autonomic responses","volume":"44","year":"2024","journal-title":"J. Neurosci."},{"key":"2025021913392163700_c23","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1182\/blood.2023023718","article-title":"Low-intensity transcranial focused ultrasound changes pain-associated behaviors by modulating pain processing brain circuits","volume":"144","year":"2024","journal-title":"Blood"},{"issue":"3","key":"2025021913392163700_c24","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.brs.2012.05.002","article-title":"Transcranial ultrasound (TUS) effects on mental states: A pilot study","volume":"6","year":"2013","journal-title":"Brain Stimul."},{"issue":"12","key":"2025021913392163700_c25","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1097\/j.pain.0000000000003322","article-title":"Noninvasive targeted modulation of pain circuits with focused ultrasonic waves","volume":"165","year":"2024","journal-title":"Pain"},{"issue":"6","key":"2025021913392163700_c26","doi-asserted-by":"publisher","first-page":"e059943","DOI":"10.1136\/bmjopen-2021-059943","article-title":"Feasibility of cognitive training in combination with transcranial direct current stimulation in a home-based context (TrainStim-Home): Study protocol for a randomised controlled trial","volume":"12","year":"2022","journal-title":"BMJ Open"},{"key":"2025021913392163700_c27","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1016\/j.jpain.2010.07.002","article-title":"The prevalence of chronic pain in United States adults: Results of an Internet-based survey","volume":"11","year":"2010","journal-title":"J. Pain"},{"issue":"3","key":"2025021913392163700_c28","doi-asserted-by":"publisher","first-page":"715","DOI":"10.3233\/JAD-190142","article-title":"Sex differences in associations of cognitive function with perceptions of pain in older adults","volume":"70","year":"2019","journal-title":"J. Alzheimer's Dis."},{"issue":"8","key":"2025021913392163700_c29","doi-asserted-by":"publisher","first-page":"e0160608","DOI":"10.1371\/journal.pone.0160608","article-title":"Comparative analysis of pain behaviours in humanized mouse models of sickle cell anemia","volume":"11","year":"2016","journal-title":"PLoS One"},{"issue":"3","key":"2025021913392163700_c30","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1182\/blood-2010-01-260372","article-title":"Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: Modulation by cannabinoids","volume":"116","year":"2010","journal-title":"Blood"},{"key":"2025021913392163700_c31","first-page":"43","article-title":"Amplifier power series and distortion","volume-title":"Analog Integrated Circuits for Communication: Principles, Simulation and Design","year":"2007","edition":"2"},{"issue":"3","key":"2025021913392163700_c32","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1109\/MMM.2021.3131834","article-title":"DC Block and RF Choke [Enigmas, etc.]","volume":"23","year":"2022","journal-title":"IEEE Microwave Mag."},{"key":"2025021913392163700_c33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1109\/TIM.2021.3125978","article-title":"Investigation of displacement of intracranial electrode induced by focused ultrasound stimulation","volume":"70","year":"2021","journal-title":"IEEE Trans. Instrum. Meas."},{"key":"2025021913392163700_c34","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1038\/s41467-021-22743-7","article-title":"Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation","volume":"12","year":"2021","journal-title":"Nat. Commun."},{"key":"2025021913392163700_c35","doi-asserted-by":"publisher","first-page":"021314","DOI":"10.1117\/1.3360308","article-title":"k-wave: MATLAB toolbox for the simulation and reconstruction of photoacoustic wave fields","volume":"15","year":"2010","journal-title":"J. Biomed. Opt."},{"issue":"2","key":"2025021913392163700_c36","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1121\/10.0013426","article-title":"Benchmark problems for transcranial ultrasound simulation: Intercomparison of compressional wave models","volume":"152","year":"2022","journal-title":"J. Acoust. Soc. Am."},{"issue":"5","key":"2025021913392163700_c37","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.neuron.2010.05.008","article-title":"Transcranial pulsed ultrasound stimulates intact brain circuits","volume":"66","year":"2010","journal-title":"Neuron"},{"issue":"12","key":"2025021913392163700_c38","doi-asserted-by":"publisher","first-page":"3376","DOI":"10.1182\/blood-2010-12-327429","article-title":"Transient receptor potential vanilloid 1 mediates pain in mice with severe sickle cell disease","volume":"118","year":"2011","journal-title":"Blood"},{"issue":"9","key":"2025021913392163700_c39","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1016\/j.mayocp.2019.03.034","article-title":"Gender differences in pain risk in old age: Magnitude and contributors","volume":"94","year":"2019","journal-title":"Mayo Clin. Proc."},{"key":"2025021913392163700_c40","doi-asserted-by":"publisher","first-page":"e2609","DOI":"10.3791\/2609","article-title":"Measuring motor coordination in mice","volume":"75","year":"2013","journal-title":"J. Vis. Exp."},{"issue":"1","key":"2025021913392163700_c41","doi-asserted-by":"publisher","first-page":"14405","DOI":"10.1038\/s41598-021-93944-9","article-title":"Quantification of early learning and movement sub-structure predictive of motor performance","volume":"11","year":"2021","journal-title":"Sci. Rep."},{"issue":"12","key":"2025021913392163700_c42","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.tins.2009.07.007","article-title":"Critical role of nociceptor plasticity in chronic pain","volume":"32","year":"2009","journal-title":"Trends Neurosci."},{"issue":"3","key":"2025021913392163700_c43","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s41999-021-00481-9","article-title":"Adverse drug reactions in older adults: A narrative review of the literature","volume":"12","year":"2021","journal-title":"Eur. Geriatr. Med."},{"issue":"10","key":"2025021913392163700_c44","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.1007\/s00221-022-06449-w","article-title":"Age-dependent effects of social isolation on mesolimbic dopamine release","volume":"240","year":"2022","journal-title":"Exp. Brain Res."},{"issue":"6","key":"2025021913392163700_c45","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1056\/NEJMra2301292","article-title":"Frailty in older adults","volume":"391","year":"2024","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"2025021913392163700_c46","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1289\/ehp.1307272","article-title":"Environmental noise pollution in the United States: Developing an effective public health response","volume":"122","year":"2014","journal-title":"Environ. Health Perspect."},{"issue":"4","key":"2025021913392163700_c47","doi-asserted-by":"publisher","first-page":"623","DOI":"10.7863\/jum.2012.31.4.623","article-title":"Bioeffects committee of the american institute of ultrasound in medicine. Overview of therapeutic ultrasound applications and safety considerations","volume":"31","year":"2012","journal-title":"J. Ultrasound Med."},{"key":"2025021913392163700_c48","volume-title":"Marketing Clearance of Diagnostic Ultrasound Systems and Transducers","author":"FDA, U. S.","year":"2019"},{"issue":"1","key":"2025021913392163700_c49","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1109\/TBME.2018.2821201","article-title":"Noninvasive ultrasonic neuromodulation in freely moving mice","volume":"66","year":"2019","journal-title":"IEEE Trans. Biomed. Eng."},{"issue":"4","key":"2025021913392163700_c50","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1016\/j.brs.2020.03.016","article-title":"Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia acutely and reduces A\u03b2 load chronically, as demonstrated in vivo","volume":"13","year":"2020","journal-title":"Brain Stimul."},{"issue":"1","key":"2025021913392163700_c51","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S0889-8545(02)00062-1","article-title":"Relieving endometriosis pain: Why is it so tough?","volume":"30","year":"2003","journal-title":"Obstet. Gynecol. Clin. North Am."},{"issue":"1","key":"2025021913392163700_c52","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s40122-021-00244-1","article-title":"Pain in women: A perspective review on a relevant clinical issue that deserves prioritization","volume":"10","year":"2021","journal-title":"Pain Ther."},{"issue":"2","key":"2025021913392163700_c53","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S0304-3959(99)00114-1","article-title":"Electrical stimulation of motor cortex for pain control: A combined PET-scan and electrophysiological study","volume":"83","year":"1999","journal-title":"Pain"},{"key":"2025021913392163700_c54","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1097\/j.pain.0000000000003297","article-title":"Prediction of the response to repetitive transcranial magnetic stimulation of the motor cortex in peripheral neuropathic pain and validation of a new algorithm","volume":"166","year":"2025","journal-title":"Pain"},{"issue":"11","key":"2025021913392163700_c55","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1016\/j.jpain.2015.07.005","article-title":"Frequency of hospitalizations for pain and association with altered brain network connectivity in sickle cell disease","volume":"16","year":"2015","journal-title":"J. Pain"},{"issue":"7","key":"2025021913392163700_c56","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/nrn3516","article-title":"Cognitive and emotional control of pain and its disruption in chronic pain","volume":"14","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"issue":"1","key":"2025021913392163700_c57","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.pneurobio.2010.10.005","article-title":"The pain matrix reloaded: A salience detection system for the body","volume":"93","year":"2011","journal-title":"Prog. Neurobiol."},{"issue":"1\u20134","key":"2025021913392163700_c58","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1159\/000101249","article-title":"Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus","volume":"46","year":"1983","journal-title":"Stereotact. Funct. Neurosurg."},{"key":"2025021913392163700_c59","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.ultras.2015.09.016","article-title":"Impedance matching network for high frequency ultrasonic transducer for cellular applications","volume":"65","year":"2016","journal-title":"Ultrasonics"},{"key":"2025021913392163700_c60","first-page":"1567","article-title":"Bipolar pulse generator for very high frequency (&gt;100 MHz) ultrasound applications","year":"2013"},{"issue":"2","key":"2025021913392163700_c61","doi-asserted-by":"publisher","first-page":"026026","DOI":"10.1088\/1741-2552\/ab6be6","article-title":"Image-guided focused ultrasound modulates electrically evoked motor neuronal activity in the mouse peripheral nervous system in vivo","volume":"17","year":"2020","journal-title":"J. Neural Eng."},{"issue":"5339","key":"2025021913392163700_c62","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1126\/science.278.5339.876","article-title":"Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease","volume":"278","year":"1997","journal-title":"Science"},{"issue":"1","key":"2025021913392163700_c63","doi-asserted-by":"publisher","first-page":"e54","DOI":"10.1002\/cpns.54","article-title":"Mouse models of pain in sickle cell disease","volume":"85","year":"2018","journal-title":"Curr. Protoc. Neurosci."},{"issue":"6","key":"2025021913392163700_c64","doi-asserted-by":"publisher","first-page":"066012","DOI":"10.1088\/1741-2552\/aa843e","article-title":"Numerical evaluation of the skull for human neuromodulation with transcranial focused ultrasound","volume":"14","year":"2017","journal-title":"J. Neural Eng."},{"key":"2025021913392163700_c65","volume-title":"Simulation Methods and Tissue Property Models for Non-Invasive Transcranial Focused Ultrasound Surgery","year":"2005"},{"key":"2025021913392163700_c66","first-page":"2995","article-title":"Combined clinical PET\/CT and MicroPET small animal imaging","year":"2004"},{"issue":"2\u20133","key":"2025021913392163700_c67","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/0304-3959(96)03048-5","article-title":"Individual differences in the hotplate test and effects of habituation on sensitivity to morphine","volume":"66","year":"1996","journal-title":"Pain"},{"issue":"2","key":"2025021913392163700_c68","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.jpain.2010.06.011","article-title":"The influence of non-nociceptive factors on hot-plate latency in rats","volume":"12","year":"2011","journal-title":"J. Pain"},{"issue":"3","key":"2025021913392163700_c69","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1590\/S0100-879X2005000300016","article-title":"A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics","volume":"38","year":"2005","journal-title":"Braz. J. Med. Biol. Res."}],"container-title":["APL Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.aip.org\/aip\/apb\/article-pdf\/doi\/10.1063\/5.0236108\/20402565\/016108_1_5.0236108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pubs.aip.org\/aip\/apb\/article-pdf\/doi\/10.1063\/5.0236108\/20402565\/016108_1_5.0236108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.aip.org\/aip\/apb\/article-pdf\/doi\/10.1063\/5.0236108\/20402565\/016108_1_5.0236108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:07:36Z","timestamp":1745352456000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.aip.org\/apb\/article\/9\/1\/016108\/3336351\/Analgesic-effect-of-simultaneously-targeting"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":69,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3,1]]}},"URL":"https:\/\/doi.org\/10.1063\/5.0236108","relation":{},"ISSN":["2473-2877"],"issn-type":[{"value":"2473-2877","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3,1]]},"published":{"date-parts":[[2025,2,19]]},"article-number":"016108"}}