title: Mas-Related Gene (Mrg) C Activation Attenuates Bone Cancer Pain via Modulating Gi and NR2B.
abstract: This study is to investigate the role of Mas-related gene (Mrg) C in the pathogenesis and treatment of bone cancer pain (BCP).
  
  
  
  BCP mouse model was established by osteosarcoma cell inoculation. Pain-related behaviors were assessed with the spontaneous lifting behavior test and mechanical allodynia test. Expression levels of MrgC, Gi, and NR2B in the spinal cord were detected with Western blot analysis and immunohistochemistry.
  
  
  
  Pain-related behavior tests showed significantly increased spontaneous flinches (NSF) and decreased paw withdrawal mechanical threshold (PWMT) in mouse models of BCP. Western blot analysis showed that, compared with the control group and before modeling, all the expression levels of MrgC, Gi, and NR2B in the spinal cord of BCP mice were dramatically elevated, which were especially increased at day 7 after operation and thereafter, in a time-dependent manner. Moreover, the treatment of MrgC agonist BAM8-22 significantly up-regulated Gi and down-regulated NR2B expression levels, in the spinal cord of BCP mice, in a time-dependent manner. On the other hand, anti-MrgC significantly down-regulated Gi expression, while dramatically up-regulated NR2B expression, in the BCP mice. Similar results were obtained from the immunohistochemical detection. Importantly, BAM8-22 significantly attenuated the nociceptive behaviors in the BCP mice.
  
  
  
  Our results indicated the MrgC-mediated Gi and NR2B expression alterations in the BCP mice, which might contribute to the pain hypersensitivity. These findings may provide a novel strategy for the treatment of BCP in clinic.
authors.affiliation: Department of Anaesthesiology, the Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu, China.
authors.forename: Yu'e
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anaesthesiology, the Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Anaesthesiology, the Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu, China.
authors.forename: Bailing
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Anaesthesiology, the Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu, China.
authors.forename: Cui'e
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Anaesthesiology, the Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu, China.
authors.forename: Yishan
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Anaesthesiology, the Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu, China.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Anaesthesiology, the Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gu
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001859:Bone Neoplasms / Q000150:complications*; D000072716:Cancer Pain / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000591604:MrgC protein, mouse; C121001:NR2B NMDA receptor; D043562:Receptors, G-Protein-Coupled; D016194:Receptors, N-Methyl-D-Aspartate; D019206:GTP-Binding Protein alpha Subunits, Gi-Go