{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:49:27Z","timestamp":1792007367272,"version":"4.4.0"},"reference-count":41,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,4,29]]},"abstract":"<jats:p>The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated neuronal plasticity in the bed nucleus of the stria terminalis (BNST), which plays a critical role in chronic pain\u2013induced maladaptive anxiety. Electrophysiology demonstrated that chronic pain increased inhibitory inputs to lateral hypothalamus (LH)\u2013projecting BNST neurons. Chemogenetic manipulation revealed that sustained suppression of LH-projecting BNST neurons played a crucial role in chronic pain\u2013induced anxiety. Furthermore, using a molecular genetic approach, we demonstrated that chronic pain elevated the excitability of a specific subpopulation of BNST neurons, which express cocaine- and amphetamine-regulated transcript (CART). The elevated excitability of CART-positive neurons caused the increased inhibitory inputs to LH-projecting BNST neurons, thereby inducing anxiety-like behavior. These findings shed light on how chronic pain induces psychiatric disorders, characterized by maladaptive anxiety.<\/jats:p>","DOI":"10.1126\/sciadv.abj5586","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T17:58:00Z","timestamp":1651082280000},"source":"Crossref","is-referenced-by-count":84,"title":["Chronic pain\u2013induced neuronal plasticity in the bed nucleus of the stria terminalis causes maladaptive anxiety"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2205-9754","authenticated-orcid":true,"given":"Naoki","family":"Yamauchi","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsaku","family":"Murakawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6172-4788","authenticated-orcid":true,"given":"Hiroshi","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-2276","authenticated-orcid":true,"given":"Taiju","family":"Amano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0144-0679","authenticated-orcid":true,"given":"Masabumi","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0007-1331.2001.00727.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.163.20.2433"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(03)00301-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/504691"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.08.004"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.021"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3195-17.2018"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.07.017"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.109"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.015"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1113\/eph8702357"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1480-08.2008"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4278-12.2013"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobeha.2018.10.003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3047-18.2019"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12018"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4057-12.2012"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10949"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14165"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05453"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201591942"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-020-00684-4"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107759"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0198-x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00004.2013"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19318"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09559"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09553"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3322"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21047"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4102"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.741895"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-020-00807-4"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108362"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12041"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01368-2"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2017.08.012"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4642"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00276-1"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.01.019"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.abj5586","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T18:21:57Z","timestamp":1704824517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.abj5586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,29]]},"references-count":41,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2022,4,29]]}},"alternative-id":["10.1126\/sciadv.abj5586"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.abj5586","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,29]]},"article-number":"eabj5586"}}