{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T01:12:16Z","timestamp":1777770736244,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82205278"],"award-info":[{"award-number":["82205278"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mental disorders frequently co\u2010occur with pain, yet pain mechanisms in non\u2010peripheral etiologies (e.g., chronic psychological stress) remain underexplored. The ventral anterior\u2013lateral thalamic complex (VAL) is implicated in emotional processing, but its role in chronic stress\u2010induced pain hypersensitivity is unclear. Electroacupuncture (EA) is clinically used for pain management, but its efficacy and mechanisms in chronic stress\u2010driven pain hypersensitivity require validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A chronic restraint stress (CRS) model was established in male mice. Behavioral assessments were performed to quantify mechanical sensitivity (hindpaws and abdomen using von Frey filaments), thermal sensitivity (hot plate test), and spontaneous pain\u2010like behaviors. Bidirectional chemogenetic approaches targeted VAL CaMKII\u03b1\u2010positive neurons. EA was applied at Zusanli (ST36) and Sanyinjiao (SP6) acupoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CRS stably induced pain hypersensitivity phenotypes, including mechanical allodynia (hindpaws\/abdomen), thermal hyperalgesia, and spontaneous pain\u2010like behaviors. Chemogenetic inhibition of VAL CaMKII\u03b1\u2010positive neurons reversed these CRS\u2010induced hypersensitivity responses. Conversely, activating these neurons in naive mice recapitulated the full spectrum of hyperalgesia phenotypes. EA alleviated CRS\u2010induced hindpaw mechanical\/thermal hyperalgesia, abdominal allodynia, and spontaneous pain. EA's effects on hindpaw mechanical\/thermal hyperalgesia were mediated by suppression of VAL CaMKII\u03b1\u2010positive neurons. In contrast, its amelioration of abdominal allodynia and spontaneous pain persisted despite chemogenetic activation of VAL CaMKII\u03b1\u2010positive neurons, indicating possible distinct pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals the pivotal role of thalamic VAL CaMKII\u03b1\u2010positive neurons in chronic stress\u2010associated pain hypersensitivity and elucidates EA's analgesic mechanisms, providing novel therapeutic strategies for emotion\u2013pain comorbidity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70855","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:40:34Z","timestamp":1757407234000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ventral Anterior\u2013Lateral Complex of the Thalamus Mediates Chronic Stress\u2010Induced Pain Hypersensitivity and Underlies Electroacupuncture Analgesia"],"prefix":"10.1002","volume":"15","author":[{"given":"Jie","family":"Chen","sequence":"first","affiliation":[{"name":"Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University\uff08Tongde Hospital of Zhejiang Province\uff09 Hangzhou China"},{"name":"Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research The Third Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinling","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research The Third Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research The Third Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research The Third Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9264-203X","authenticated-orcid":false,"given":"Zui","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research The Third Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peipei","family":"Feng","sequence":"additional","affiliation":[{"name":"Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University\uff08Tongde Hospital of Zhejiang Province\uff09 Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"52","article-title":"Pain in Times of Stress","volume":"22","author":"Ahmad A. H.","year":"2015","journal-title":"Malaysian Journal of Medical Sciences"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42234\u2010023\u201000130\u20105"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.07.005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.30906"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2639"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003433"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn894"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/pr9.0000000000000575"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106907"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1243232"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.add4391"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2008.09.013"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429\u2010022\u201002582\u2010y"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010024\u201007372\u20102"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/psy.0000000000000779"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.05.014"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.09.002"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpain.2022.869884"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2010.03.006"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000002006"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013536\u20100"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201056258\u20102"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010008\u20109692\u2010y"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/09645284221107699"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.960868"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/09638288.2020.1850888"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(21)00359\u20107"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/516851"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.615395"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042814\u20101"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.22744"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3109\/08990221003646736"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2008.10.021"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020\u2010025\u201001083\u20104"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2025.03.027"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806919850383"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro\u20102023\u20100037"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000527276"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24880"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70855","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.70855","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70855","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:39:30Z","timestamp":1777480770000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.70855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":39,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/brb3.70855"],"URL":"https:\/\/doi.org\/10.1002\/brb3.70855","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BRB3.70855\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70855\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70855\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70855\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70855\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70855\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70855\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70855\/v2\/review1","asserted-by":"object"}]},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70855"}}