{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:52:34Z","timestamp":1789674754904,"version":"4.0.1"},"reference-count":75,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"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":["82371536"],"award-info":[{"award-number":["82371536"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401444"],"award-info":[{"award-number":["82401444"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201361"],"award-info":[{"award-number":["82201361"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81300957"],"award-info":[{"award-number":["81300957"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171227"],"award-info":[{"award-number":["82171227"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501479"],"award-info":[{"award-number":["82501479"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Chronic pain is a widespread and debilitating condition with limited treatment options. While the ventral tegmental area (VTA) and posterior hypothalamic nucleus (PH) have been independently implicated in pain modulation, the specific neural circuitry linking them remains unclear. This study aimed to investigate the role of the PH\u2009\u2192\u2009VTA glutamatergic projection in chronic pain regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Using a mouse model of neuropathic pain induced by chronic constriction injury (CCI), we combined viral tracing, immunofluorescence, in vitro electrophysiology, optogenetics, chemogenetics and fibre photometry. Behavioural assays were used to assess mechanical allodynia and thermal hyperalgesia following circuit manipulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>We identified a glutamatergic projection from PH to VTA dopamine (DA) neurons that modulates pain behaviour. Optogenetic activation of the PH\u2009\u2192\u2009VTA circuit in na\u00efve mice induced pain\u2010like hypersensitivity. Conversely, inhibition of this pathway reduced pain\u2010related behaviours in CCI mice. Mechanistically, PH activation increased glutamatergic input onto VTA DA neurons, enhancing dopamine release in the nucleus accumbens (NAc). Fibre photometry confirmed increased activity in this circuit during nociceptive states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      Our results define a functional PH\n                      <jats:sup>Glu<\/jats:sup>\n                      \u2009\u2192\u2009VTA\n                      <jats:sup>DA<\/jats:sup>\n                      \u2009\u2192\u2009NAc circuit that contributes to chronic pain processing. Hyperactivity in this pathway facilitates nociceptive behaviours, while its inhibition exerts analgesic effects. Modulating this circuit may offer new therapeutic strategies for treating chronic pain.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70227","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:20:55Z","timestamp":1763356855000},"page":"1427-1444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A posterior hypothalamic to midbrain circuit orchestrating nociceptive behaviours in male mice"],"prefix":"10.1111","volume":"183","author":[{"given":"Yu","family":"Ma","sequence":"first","affiliation":[{"name":"Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education  Shanghai China"},{"name":"Department of Anaesthesiology Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer Institute  Shanghai China"},{"name":"Songjiang Hospital and Songjiang Research Institute &amp; Shanghai Key Laboratory of Emotions and Affective Disorders Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7158-6605","authenticated-orcid":false,"given":"Weinan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education  Shanghai China"},{"name":"Department of Anesthesiology, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education  Shanghai China"},{"name":"Department of Anesthesiology, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipesh","family":"Chaudhury","sequence":"additional","affiliation":[{"name":"Health &amp; Cognition Theme, Center for Brain &amp; Health New York University Abu Dhabi (NYUAD)  Abu Dhabi United\u00a0Arab\u00a0Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Clinical Research Center for Anesthesia and Perioperative Medicine Huzhou Central Hospital  Huzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education  Shanghai China"},{"name":"Department of Anesthesiology, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education  Shanghai China"},{"name":"Department of Anesthesiology, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.1083671"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-8993(00)03015-8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90965-p"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2014.07.016"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102411409070"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.02.005"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.015"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000013253"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibror.2018.05.001"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-26"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12643"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0409-15.2015"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab754"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)00393-7"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458509107018"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1103"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20206"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro.2008.19.4-5.227"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.03.003"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91402-e"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2006.01.005"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(95)00129-8"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.75718"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-27610-7"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.07.006"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12576-022-00846-0"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.04.053"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00040.2019"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3322"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.08.024"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2016.24"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2298-22.2023"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.13-06-02689.1993"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00924-3"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2004.04141.x"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105749"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-006-0589-8"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.2147\/tcrm.S37592"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.06.027"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2012.00063"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.07.018"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03879-8"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419839992"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"issue":"4","key":"e_1_2_12_52_1","first-page":"499","article-title":"Pain relief after hypophysectomy","volume":"14","author":"Ramirez L. F.","year":"1984","journal-title":"Neurosurgery"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002092"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.06.003"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-2236(00)02002-6"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.03.021"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2020-059577"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-020-01098-2"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynpai.2017.04.003"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44254-024-00077-z"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-00981-9"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1417.027"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000494"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/ner.12869"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.neu.0000345937.05186.73"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01922-y"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-021-00668-x"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.017"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.033"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.02.013"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.29.620973"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.10.032"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.02.1180"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02488-7"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808622115"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2024.102458"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70227","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70227","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:22:28Z","timestamp":1773030148000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,16]]},"references-count":75,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/bph.70227"],"URL":"https:\/\/doi.org\/10.1111\/bph.70227","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,16]]},"assertion":[{"value":"2025-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}