{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:21:37Z","timestamp":1788459697200,"version":"build-2803163510"},"reference-count":72,"publisher":"Society for Neuroscience","issue":"9","license":[{"start":{"date-parts":[[2027,3,1]],"date-time":"2027-03-01T00:00:00Z","timestamp":1803859200000},"content-version":"vor","delay-in-days":200,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"crossref","award":["5R01DC016559"],"award-info":[{"award-number":["5R01DC016559"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100002046","name":"Hearing Health Foundation","doi-asserted-by":"publisher","award":["Emerging Research Grant"],"award-info":[{"award-number":["Emerging Research Grant"]}],"id":[{"id":"10.13039\/100002046","id-type":"DOI","asserted-by":"publisher"}]},{"name":"David M. Rubenstein Precision Medicine Center of Excellence in Hearing Fund","award":["Project 2a"],"award-info":[{"award-number":["Project 2a"]}]},{"name":"David M. Rubenstein Professorship"},{"name":"Blaustein Pain Research Fund Grant"},{"name":"John Mitchell Jr. Fund"},{"name":"Geraldine Dietz Fox Endowed Research Fund"}],"content-domain":{"domain":["eneuro.org"],"crossmark-restriction":true},"short-container-title":["eNeuro"],"accepted":{"date-parts":[[2026,8,10]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Humans can experience sound-evoked pain, either from extremely loud sounds or in cases of pain hyperacusis from typically tolerable sounds. However, the mechanisms underlying sound-evoked pain remain poorly understood. Developing behavioral methods to measure sound-evoked pain in animal models is critical for elucidating these mechanisms. Here, a machine learning-based approach was developed to measure sound-evoked pain in freely moving mice of both sexes by analyzing facial grimace and body position from video recordings during sound exposure. Facial grimace, a commonly used method to detect pain in mice, and body position, which can be used to measure postural and movement changes that also indicate pain, were both quantified using a deep neural network model trained to extract established facial and body features from video recorded by a single camera. To validate the model's capability to detect pain, a known painful state, migraine induced by the injection of the neuropeptide calcitonin gene-related peptide (CGRP), was used. Using this machine learning-based approach, the ability to quantify a pain response from CGRP-induced migraine, distinct from baseline behavior, was demonstrated, resulting in a defined pain threshold. Sound exposures at high intensities elicited significant changes in facial grimace and body position, in comparison, surpassing the pain threshold calculated from CGRP-induced migraine. These behavioral changes were absent in\n                    <jats:italic>Tmie<\/jats:italic>\n                    -knock-out mice, which lack functional sound transduction in the cochlea. This automated, high-throughput framework enables objective and sensitive analysis of pain-related behavior providing a foundation for future studies investigating the peripheral and central mechanisms of sound-evoked pain.\n                  <\/jats:p>","DOI":"10.1523\/eneuro.0064-26.2026","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:50:12Z","timestamp":1786643412000},"page":"ENEURO.0064-26.2026","update-policy":"https:\/\/doi.org\/10.1523\/eneuro.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Machine Learning-Guided Video Analysis Identifies Sound-Evoked Pain-Related Behaviors from Facial Grimace and Body Cues in Mice"],"prefix":"10.1523","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9585-935X","authenticated-orcid":false,"given":"Benjamin J.","family":"Seicol","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Valles-Jane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Glowatzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7405-8067","authenticated-orcid":false,"given":"Megan B.","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-98184-9"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2012.05.008"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fneur.2020.00014","article-title":"Tympanic resonance hypothesis","volume":"11","author":"Boedts","year":"2020","journal-title":"Front Neurol"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.06.008"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.5","doi-asserted-by":"crossref","first-page":"10899","DOI":"10.1038\/s41467-024-55275-x","article-title":"Defects in hair cells disrupt the development of auditory peripheral circuitry","volume":"15","author":"Bottom","year":"2024","journal-title":"Nat Commun"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.6","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3390\/jpm12060851","article-title":"Deep learning-based grimace scoring is comparable to human scoring in a mouse migraine model","volume":"12","author":"Chiang","year":"2022","journal-title":"J Pers Med"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2024.02.057"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.01.016"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.9","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3758\/BF03209686","article-title":"Persistent effect of noise on the acoustic startle reflex in the rat","volume":"7","author":"Cory","year":"1979","journal-title":"Anim Learn Behav"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.10","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00284"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.11","doi-asserted-by":"publisher","DOI":"10.1177\/0023677219881655"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.11.051"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210849119"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.14","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01023.2011"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.01.009"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.16","doi-asserted-by":"crossref","first-page":"108509","DOI":"10.1016\/j.heares.2022.108509","article-title":"Contraction of the stapedius and tensor tympani muscles explored by tympanometry and pressure measurement in the external auditory canal","volume":"420","author":"Fournier","year":"2022","journal-title":"Hear Res"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.17","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(96)00083-4"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.18","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902400206"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911632106"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.20","doi-asserted-by":"crossref","first-page":"12240","DOI":"10.1038\/s41598-021-91444-4","article-title":"Automated home-cage for the evaluation of innate non-reflexive pain behaviors in a mouse model of inflammatory pain","volume":"11","author":"Hasriadi","year":"2021","journal-title":"Sci Rep"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.21","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.neuroscience.2019.07.028","article-title":"Introducing a mammalian nerve-muscle preparation ideal for physiology and microscopy, the transverse auricular muscle in the ear of the mouse","volume":"439","author":"Heuser","year":"2020","journal-title":"Neuroscience"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.22","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00184.2013"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.23","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-021-00808-0"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.24","doi-asserted-by":"crossref","first-page":"104741","DOI":"10.1016\/j.jpain.2024.104741","article-title":"Clinical phenotype and management of sound-induced pain: insights from adults with pain hyperacusis","volume":"27","author":"Jahn","year":"2025","journal-title":"J Pain"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.25","first-page":"448","article-title":"Effect of pain management on immunization efficacy in mice","volume":"51","author":"Kolstad","year":"2012","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1455"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.27","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2002.00310.x"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.28","doi-asserted-by":"crossref","first-page":"ENEURO.0349-22.2022","DOI":"10.1523\/ENEURO.0349-22.2022","article-title":"A new tool for quantifying mouse facial expressions","volume":"10","author":"Le Mo\u00ebne","year":"2023","journal-title":"eNeuro"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0240431"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515228112"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2017.07.001"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.32","doi-asserted-by":"crossref","first-page":"108012","DOI":"10.1016\/j.heares.2020.108012","article-title":"Interaction of auditory and pain pathways: effects of stimulus intensity, hearing loss and opioid signaling","volume":"393","author":"Manohar","year":"2020","journal-title":"Hear Res"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.33","doi-asserted-by":"crossref","first-page":"108726","DOI":"10.1016\/j.heares.2023.108726","article-title":"Chronic stress induced loudness hyperacusis, sound avoidance and auditory cortex hyperactivity","volume":"431","author":"Manohar","year":"2023","journal-title":"Hear Res"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2967-16.2016"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0209-y"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.36","doi-asserted-by":"publisher","DOI":"10.1097\/J.PAIN.0000000000003187"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.37","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80015"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.38","doi-asserted-by":"publisher","DOI":"10.1177\/1084713810381771"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.39","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/BF00456661","article-title":"Encapsulated nerve corpuscles in the human tympanic membrane","volume":"246","author":"Nagai","year":"1989","journal-title":"Arch Otorhinolaryngol"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0176-0"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.41","unstructured":"National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals (2010) Recognition and alleviation of pain in laboratory animals . Washington (DC): National Academies Press (US)."},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.42","doi-asserted-by":"crossref","first-page":"ENEURO.0383-21.2021","DOI":"10.1523\/ENEURO.0383-21.2021","article-title":"Prior acoustic trauma alters type II afferent activity in the mouse cochlea","volume":"8","author":"Nowak","year":"2021","journal-title":"eNeuro"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.43","doi-asserted-by":"publisher","DOI":"10.1044\/2014_AJA-13-0037"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/01.HJ.0000602900.16223.0e","article-title":"Clinical advancements for managing hyperacusis with pain","volume":"72","author":"Pollard","year":"2019","journal-title":"Hear J"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.45","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1080\/00016489.2024.2413385","article-title":"The quantification and mRNA expression levels of cochlear synapses in C57BL\/6j mice following repeated exposure to noise","volume":"144","author":"Qian","year":"2024","journal-title":"Acta Otolaryngol"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.46","doi-asserted-by":"crossref","first-page":"108026","DOI":"10.1016\/j.heares.2020.108026","article-title":"Using auditory reaction time to measure loudness growth in rats","volume":"395","author":"Radziwon","year":"2020","journal-title":"Hear Res"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.47","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001337"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.48","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.mehy.2013.02.021","article-title":"Chorda tympani nerve, may it have a role in stabilizing middle ear pressure?","volume":"80","author":"Rinaldi","year":"2013","journal-title":"Med Hypotheses"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.49","doi-asserted-by":"publisher","DOI":"10.3109\/00016489209137479"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.50","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.heares.2015.10.005","article-title":"Untangling the effects of tinnitus and hypersensitivity to sound (hyperacusis) in the gap detection test","volume":"331","author":"Salloum","year":"2016","journal-title":"Hear Res"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.51","doi-asserted-by":"crossref","first-page":"108648","DOI":"10.1016\/j.heares.2022.108648","article-title":"Hyperacusis: loudness intolerance, fear, annoyance and pain","volume":"426","author":"Salvi","year":"2022","journal-title":"Hear Res"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.52","doi-asserted-by":"publisher","DOI":"10.1121\/10.0016593"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.53","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1152\/jn.00024.2024","article-title":"The vestigial pinna-orienting system in humans briefly suppresses superior auricular muscle activity during reflexive orienting toward auditory stimuli","volume":"132","author":"Schroeer","year":"2024","journal-title":"J Neurophysiol"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.54","doi-asserted-by":"publisher","DOI":"10.3766\/jaaa.16.2.4"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.55","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adp1934"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.56","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-013-0555-1"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.57","doi-asserted-by":"crossref","first-page":"317","DOI":"10.14573\/altex.2011.4.317","article-title":"Assessment of stress in laboratory beagle dogs constrained by a Pavlov sling","volume":"28","author":"Stracke","year":"2011","journal-title":"ALTEX"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2009.09.019"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.59","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(94)90130-9"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.60","unstructured":"Sutton AE , De Jong R , Kwartowitz G (2025) Tensor tympani syndrome. In: Statpearls . Treasure Island, FL: StatPearls Publishing."},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.61","doi-asserted-by":"publisher","DOI":"10.30802\/AALAS-CM-19-000042"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.62","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918763658"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.63","doi-asserted-by":"publisher","DOI":"10.1044\/2014_AJA-14-0010"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.64","unstructured":"von Gierke HE , Brown DR (1953) Wright-Patterson AFB, Ohio. Benox report; an exploratory study of the biological effects of noise 47."},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.65","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-0963-6"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02318-2"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.67","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4103\/1463-1741.110295","article-title":"Tonic tensor tympani syndrome in tinnitus and hyperacusis patients: a multi-clinic prevalence study","volume":"15","author":"Westcott","year":"2013","journal-title":"Noise Health"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.68","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-020-00777-w"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.69","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4449"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.70","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1002\/9780470172537.ch123","article-title":"Hearing thresholds","volume":"3","author":"Yost","year":"1997","journal-title":"Encycl Acoust"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.71","doi-asserted-by":"publisher","DOI":"10.1097\/J.PAIN.0000000000002680"},{"key":"2026090310550773000_13.9.ENEURO.0064-26.2026.72","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn4663"}],"container-title":["eneuro"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/ENEURO.0064-26.2026","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/ENEURO.0064-26.2026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:55:21Z","timestamp":1788458121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eneuro.org\/lookup\/doi\/10.1523\/ENEURO.0064-26.2026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":72,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,3]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1523\/ENEURO.0064-26.2026"],"URL":"https:\/\/doi.org\/10.1523\/eneuro.0064-26.2026","relation":{},"ISSN":["2373-2822"],"issn-type":[{"value":"2373-2822","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}