{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:46:28Z","timestamp":1791413188189,"version":"4.3.3"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974168"],"award-info":[{"award-number":["81974168"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Communication within glial cells acts as a pivotal intermediary factor in modulating neuroimmune pathology. Meanwhile, an increasing awareness has emerged regarding the detrimental role of glial cells and neuroinflammation in morphine tolerance (MT). This study investigated the influence of crosstalk between astrocyte and microglia on the evolution of morphine tolerance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sprague\u2010Dawley rats were intrathecally treated with morphine twice daily for 9\u2009days to establish morphine\u2010tolerant rat model. Tail\u2010flick latency test was performed to identify the analgesic effect of morphine. The role of microglia, astrocyte and C3\u2010C3aR axis in morphine tolerance were elucidated by real\u2010time quantitative polymerase chain reaction, Western blot, and immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chronic morphine treatment notably promoted the activation of microglia, upregulated the production of proinflammatory mediators (interleukin\u20101 alpha (IL\u20101\u03b1), tumor necrosis factor alpha (TNF\u03b1), and complement component 1q (C1q)). Simultaneously, it programed astrocytes to a pro\u2010inflammatory phenotype (A1), which mainly expresses complement 3 (C3) and serping1. PLX3397 (a colony\u2010stimulating factor 1 receptor (CSF1R) inhibitor), Compstain (a C3 inhibitor) and SB290157(a C3aR antagonist) could reverse the above pathological process and alleviate morphine tolerance to different extents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings identify C3\u2010C3aR axis as an amplifier of microglia\u2010astrocyte crosstalk, neuroinflammation and a node for therapeutic intervention in morphine tolerance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70216","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T03:23:02Z","timestamp":1736738582000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<scp>C3<\/scp>\n                    \/\n                    <scp>C3aR<\/scp>\n                    Bridges Spinal Astrocyte\u2010Microglia Crosstalk and Accelerates Neuroinflammation in Morphine\u2010Tolerant Rats"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-873X","authenticated-orcid":false,"given":"Xiaoling","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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