title: Sinomenine attenuates chronic inflammatory pain in mice.
abstract: Sinomenine, an alkaloid originally isolated from the roots of Sinomeniumacutum, is used as a traditional Chinese medicine for rheumatic arthritis. However, little is known about the neuronal mechanisms underlying the analgesic effects of sinomenine in animals with chronic inflammatory pain. In this study, we investigated the persistent inflammatory pain induced by hind paw injection of complete Freund's adjuvant (CFA) in mice, which was reversed by sinomenine administration. In the anterior cingulate cortex (ACC), a region highly associated with chronic pain processing, the upregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors and Ca2+/calmodulin-dependent protein kinase II, total levels of GluA1, and phosphorylation of GluA1 at Ser831 (p-GluA1-Ser831) were reversed by systemically administrating sinomenine. Furthermore, sinomenine treatment downregulated the mammalian target of rapamycin (mTOR) pathway. Increases in p-mTOR, p-p70S6k, p-S6, and p-4EBP, which were induced by chronic inflammation, were all changed. However, sinomenine did not affect the levels of GluN2A-containing NMDA receptors and p-GluA1-Ser845, as well as the total levels of mTOR, p70S6k, S6, and 4EBP. In conclusion, results indicated that sinomenine reduced the chronic inflammatory pain induced by CFA, at least partially by regulating the GluN2B receptors and mTOR signals in the ACC.
authors: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Shuo
authors: S
authors: Li
authors: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Jing
authors: J
authors: Han
authors: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing, 210002, China.
authors: Dong-Sheng
authors: DS
authors: Wang
authors: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Qi
authors: Q
authors: Yang
authors: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Bin
authors: B
authors: Feng
authors: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing, 210002, China.
authors: Wen-Bo
authors: WB
authors: Kang
authors: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors: Le
authors: L
authors: Yang
authors: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing, 210002, China. liugene@hotmail.com.
authors: Gang
authors: G
authors: Liu
authors: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China. minggao@fmmu.edu.cn.
authors: Ming-Gao
authors: MG
authors: Zhao
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D059350:Chronic Pain / Q000139:chemically induced / Q000188:drug therapy*; D005620:Freund's Adjuvant; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D009019:Morphinans / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000700:Analgesics; D009019:Morphinans; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; C009271:sinomenine; D005620:Freund's Adjuvant; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Anterior cingulate cortex; Chronic pain; NMDA receptor; Sinomenine; mTOR