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The neural circuit mechanism underlying the chronic pain\/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVP<jats:sup>Glu<\/jats:sup>) send signals to GABAergic neurons (VLPAG<jats:sup>GABA<\/jats:sup>) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVA<jats:sup>Glu<\/jats:sup>) send signals to the nucleus accumbens D1\u2010positive neurons and D2\u2010positive neurons (NAc<jats:sup>D1\u2192D2<\/jats:sup>), which is involved in depression\u2010like behavior in comorbidity. This study demonstrates that the distinct thalamo\u2010subcortical circuits PVP<jats:sup>Glu<\/jats:sup>\u2192VLPAG<jats:sup>GABA<\/jats:sup> and PVA<jats:sup>Glu<\/jats:sup>\u2192NAc<jats:sup>D1\u2192D2<\/jats:sup> mediated painful behavior and depression\u2010like behavior following spared nerve injury (SNI), respectively, which provides the circuit\u2010based potential targets for preventing and treating comorbidity.<\/jats:p>","DOI":"10.1002\/advs.202401855","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T01:29:31Z","timestamp":1720402171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Distinct Thalamo\u2010Subcortical Circuits Underlie Painful Behavior and Depression\u2010Like Behavior Following Nerve Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"Jie","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Physiology and Pain Research 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