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It is of great significance to improve the therapies of cancer-induced bone pain due to the opioids\u2019 side effects including addiction, sedation, pruritus, and vomiting. Sinomenine, a traditional Chinese medicine, showed obvious analgesic effects on a rat model of chronic inflammatory pain, but has never been proven to treat cancer-induced bone pain. In the present study, we investigated the analgesic effect of sinomenine after tumor cell implantation and specific cellular mechanisms in cancer-induced bone pain. Our results indicated that single administration of sinomenine significantly and dose-dependently alleviated mechanical allodynia in rats with cancer-induced bone pain and the effect lasted for 4\u2009h. After tumor cell implantation, the protein levels of phosphorylated-Janus family tyrosine kinase 2 (p-JAK2), phosphorylated-signal transducers and activators of transcription 3 (p-STAT3), phosphorylated-Ca2+\/calmodulin-dependent protein kinase II (p-CAMKII), and phosphorylated-cyclic adenosine monophosphate response element-binding protein (p-CREB) were persistently up-regulated in the spinal cord horn. Chronic intraperitoneal treatment with sinomenine markedly suppressed the activation of microglia and effectively inhibited the expression of JAK2\/STAT3 and CAMKII\/CREB signaling pathways. We are the first to reveal that up-regulation of microglial JAK2\/STAT3 pathway are involved in the development and maintenance of cancer-induced bone pain. Moreover, our investigation provides the first evidence that sinomenine alleviates cancer-induced bone pain by inhibiting microglial JAK2\/STAT3 and neuronal CAMKII\/CREB cascades.<\/jats:p>","DOI":"10.1177\/1744806918793232","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T07:55:11Z","timestamp":1532073311000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":49,"title":["Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2\/STAT3 and neuronal CAMKII\/CREB cascades in rat models"],"prefix":"10.1177","volume":"14","author":[{"given":"Shu-Ping","family":"Chen","sequence":"first","affiliation":[{"name":"Anesthesiology Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science 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