title: Functional up-regulation of P2X3 receptors in dorsal root ganglion in a rat model of bone cancer pain.
abstract: BACKGROUND
  Cancer-induced bone pain remains a clinical challenge due to the poor understanding of the mechanisms. Recent study revealed extracellular adenosine triphosphate (ATP) and P2X receptors may be implicated in nociceptive signalling under cancer pain state. Therefore, here we investigated the potential role of P2X(3) receptor in a rat model of bone cancer pain.
  
  
  METHODS
  Walker 256 tumour cells were inoculated into the left tibia of Wistar rats. The model was verified by X-ray imaging, pathology and behaviour examinations. The expression of P2X(3) receptors in dorsal root ganglia (DRG) was examined. Functional significance of altered P2X(3) receptors was investigated by measuring influx upon α,β-meATP stimulation in acutely dissociated DRG neurons. Moreover, A-317491, an antagonist of P2X(3) receptors, was administrated intrathecally or locally to evaluate its analgesia effect in the cancer pain animals.
  
  
  RESULTS
  The P2X(3) receptor was up-regulated for about 50% in DRG neurons in rats with bone cancer at both protein and mRNA levels and correlated with the pain behaviour in bone cancer rats. A 51.9% increase of α,β-me ATP (10 μM, for 4 s) evoked transient response currents and a higher percentage of neurons responsive to the application of α,β-me ATP was detected in bone cancer rats. Intrathecal or local injection of A-317491 significantly attenuated pain behaviour induced by bone cancer.
  
  
  CONCLUSIONS
  These results suggest that the P2X(3) receptor is functionally up-regulated in DRG in cancer rats. P2X(3) receptor is a promising target for therapeutic intervention in cancer patients for pain management.
authors.affiliation: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: J X
authors.initials: JX
authors.lastname: Wu
authors.forename: M Y
authors.initials: MY
authors.lastname: Xu
authors.forename: X R
authors.initials: XR
authors.lastname: Miao
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Lu
authors.forename: X M
authors.initials: XM
authors.lastname: Yuan
authors.forename: X Q
authors.initials: XQ
authors.lastname: Li
authors.forename: W F
authors.initials: WF
authors.lastname: Yu
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001859:Bone Neoplasms / Q000150:complications* / Q000378:metabolism; D001842:Bone and Bones; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D020869:Gene Expression Profiling; D059352:Musculoskeletal Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000627:therapeutic use; D011083:Polycyclic Compounds / Q000627:therapeutic use; D058920:Purinergic P2X Receptor Antagonists / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C470346:A-317491; D010636:Phenols; D011083:Polycyclic Compounds; D058920:Purinergic P2X Receptor Antagonists; D012333:RNA, Messenger; D058477:Receptors, Purinergic P2X3