{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:54:00Z","timestamp":1777949640547,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Microglial activation plays a role in driving chronic migraine (CM). Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in brain microglia and impacts neuroinflammation in nervous system diseases. However, its role in CM is unclear. Here, we have investigated the role of microglial TREM2 in the development of CM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We used male mice receiving repeated intraperitoneal nitroglycerin (NTG) injections as a CM model. Mechanical and thermal hypersensitivity were assessed by mechanical withdrawal threshold and thermal withdrawal latency. TREM2 knockout mice (TREM2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) and systemically administered TREM2 agonist COG1410 were evaluated for TREM2's role in CM. TREM2, calcitonin gene\u2010related peptide (CGRP) and c\u2010fos expression in the trigeminal nucleus caudalis (TNC) were measured for central sensitisation assessment. Immunohistochemical analyses and western blots measured protein expression in the TNC and BV\u20102 microglia. Quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) detected inflammatory factor expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Recurrent NTG injection up\u2010regulated TNC protein levels of TREM2, CGRP and c\u2010fos. TREM2 loss accelerated NTG\u2010induced CM development, increased CGRP and c\u2010fos expression, and inhibited TNC autophagy. Conversely, COG1410 prevented hyperalgesia and reduced CGRP\/c\u2010fos expression in the TNC after recurrent NTG administration. In vitro, TREM2 knockdown enhanced the expression of inflammation\u2010related genes and the mTOR\/p70s6k pathway activation in lipopolysaccharide (LPS)\u2010stimulated BV\u20102 microglia, whereas COG1410 significantly inhibited LPS\u2010induced mTOR\/p70s6k pathway activation and alleviated inflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These data show that TREM2 plays a protective role in CM by modulating microglial activation and autophagy in the TNC via the mTOR\/p70s6k pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70353","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:45:52Z","timestamp":1770857152000},"page":"2803-2819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TREM2 activation suppresses central sensitisation by promoting autophagy in a chronic migraine model with recurrent nitroglycerin stimulation in mice"],"prefix":"10.1111","volume":"183","author":[{"given":"Suifa","family":"Hu","sequence":"first","affiliation":[{"name":"Nanchang Hongdu Hospital of Traditional Chinese Medicine  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiamin","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanchang Hongdu Hospital of Traditional Chinese Medicine  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University; The First Affiliated Hospital of Southern University of Science and Technology)  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sufang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixian","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiwen","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department for Bipolar Disorders Shenzhen Kangning Hospital, Shenzhen Mental Health Center  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baodong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rikang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","first-page":"S27","article-title":"The Concise Guide to PHARMACOLOGY 2021\/22: G protein\u2010coupled receptors","volume":"178","author":"Alexander S. P.","year":"2021","journal-title":"British Journal of Pharmacology"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"S313","article-title":"The Concise Guide to PHARMACOLOGY 2021\/22: Enzymes","volume":"178","author":"Alexander S. P.","year":"2021","journal-title":"British Journal of Pharmacology"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01853-x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1644076"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0942-2"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03313-2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14625"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2012.02249.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1459-7"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1841953"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13529"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000831"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-02056-0"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1603-4"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01302-x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73939"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.08.008"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2009.06.012"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1556946"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135552"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.10.004"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02300-1"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918767697"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01707-w"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105586"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.023"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18007"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01991-2"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02342-5"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-022-01496-8"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02651-3"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03875-x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06579-9"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1610-5"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70353","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70353","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70353","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:20:21Z","timestamp":1777864821000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":37,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/bph.70353"],"URL":"https:\/\/doi.org\/10.1111\/bph.70353","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"assertion":[{"value":"2025-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}