title: Upregulation of (C-X-C motif) Ligand 13 (CXCL13) Attenuates Morphine Analgesia in Rats with Cancer-Induced Bone Pain.
abstract: BACKGROUND
  The aim of this study was to investigate the role of chemokine (C-X-C motif) ligand 13 (CXCL13) in morphine tolerance in rats with cancer-induced bone pain (CIBP).
  MATERIAL AND METHODS
  We established a rat CIBP model and a rat CIBP-morphine tolerance (BM) model. BM rats were intrathecally administered rmCXCL13, neutralizing anti-CXCL13, and normal saline, while the control group rats underwent a sham operation and were injected with normal saline. The morphine analgesia was assessed by measuring mechanical withdrawal threshold (MWT) and mechanical withdrawal duration (MWD) at various time points. The co-expressions of CXCL13 and NeuN were measured by immunofluorescence double-staining. CXCL13 protein and mRNA expressions were detected by Western blot and quantitative real-time polymerase chain reaction (RT-qPCR), respectively.
  RESULTS
  Compared to the sham-operation (S) group, the BM group showed obviously decreased MWT and increased MWD on Day 9 after CIBP, but obviously increased MWT and decreased MWD on Day 3 after morphine administration; subsequently, the MWT was decreased and MWD was increased (all P<0.05). In comparison with the S+saline group, increased MWT and decreased MWD were observed in BM rats on Day 3 after anti-CXCL13 administration, and obviously decreased MWT and increased MWD were found in BM rats on Day 3 after rmCXCL13 administration (all P<0.05).
  CONCLUSIONS
  Up-regulated CXCL13 has a negative role in morphine analgesia in relief of CIBP, which may provide a new target for the management of CIBP.
authors.affiliation: Department of Pathology, South Medical District of Linyi People's Hospital, Linyi, Shandong, China (mainland).
authors.forename: Shi-Feng
authors.initials: SF
authors.lastname: Wang
authors.affiliation: Department of Pathology, Yantaishan Hospital, Yantai, Shandong, China (mainland).
authors.forename: Cheng-Gong
authors.initials: CG
authors.lastname: Dong
authors.affiliation: Pediatric Rescue Room, Linyi People's Hospital, Linyi, Shandong, China (mainland).
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Health Management Center, Qingdao Hiser Medical Group, Qingdao, Shandong, China (mainland).
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yin
mesh_terms: D000698:Analgesia / Q000379:methods; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000072716:Cancer Pain / Q000188:drug therapy* / Q000503:physiopathology; D054382:Chemokine CXCL13 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D004195:Disease Models, Animal; D004361:Drug Tolerance; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009020:Morphine / Q000494:pharmacology*; D059408:Pain Management / Q000379:methods*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D054382:Chemokine CXCL13; D012333:RNA, Messenger; D009020:Morphine