title: Intrathecal injection of metabotropic glutamate receptor subtype 3 and 5 agonist/antagonist attenuates bone cancer pain by inhibition of spinal astrocyte activation in a mouse model.
abstract: BACKGROUND
  Astrocytes and metabotropic glutamate receptors play important roles in nociceptive processing. However, their roles in bone cancer pain were not well understood. This study sought to investigate whether selective mGluR3 and mGluR5 agonist or antagonist develop antinociceptive effects on bone cancer pain by inhibition of spinal astrocyte activation.
  
  
  METHODS
  C3H/HeNCrlVr mice were inoculated into the intramedullary space of the femur with sarcoma NCTC 2472 cells to induce bone cancer pain. Quantitative real-time reverse transcription-polymerase chain reaction and Western blot experiments examined messenger RNA and protein expression of spinal glial fibrillary acidic protein, mGluR3, and mGluR5. The authors further investigated effects of intrathecal treatment with the mGluR3 agonist (APDC), the mGluR3 antagonist (LY341495), the mGluR5 agonist (CHPG), or the mGluR5 antagonist (MTEP) on nociceptive behaviors and spinal astrocyte activation associated with bone cancer pain.
  
  
  RESULTS
  Inoculation of sarcoma cells, but not α-MEM solution, induced progressive bone cancer pain and resulted in up-regulation of glial fibrillary acidic protein, mGluR3, and mGluR5 expression on days 10, 14, and 21 postinoculation. Intrathecal administration of APDC and MTEP attenuated bone cancer-evoked spontaneous pain, mechanical allodynia, thermal hyperalgesia, and reduced spinal glial fibrillary acidic protein expression. However, treatment with LY341495 and CHPG induced thermal hyperalgesia and spinal glial fibrillary acidic protein expression in control mice.
  
  
  CONCLUSIONS
  Spinal mGluR3 activation or mGluR5 inhibition reduced bone cancer pain. Inhibition of spinal astrocyte activation may contribute to the analgesic effects. These findings may lead to novel strategies for the treatment of bone cancer pain.
authors: Department of Anesthesiology, Drum-Tower Hospital, Medical School, Nanjing University, Nanjing, Jiangsu Province, China.
authors: Bing-xu
authors: BX
authors: Ren
authors: Xiao-ping
authors: XP
authors: Gu
authors: Ya-guo
authors: YG
authors: Zheng
authors: Cheng-long
authors: CL
authors: Liu
authors: Dan
authors: D
authors: Wang
authors: Yu-e
authors: YE
authors: Sun
authors: Zheng-liang
authors: ZL
authors: Ma
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000150:complications* / Q000473:pathology; D045744:Cell Line, Tumor; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006614:Hindlimb / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000150:complications* / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology; D010812:Physical Stimulation; D060888:Real-Time Polymerase Chain Reaction; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects
chemical_list: D005904:Glial Fibrillary Acidic Protein; C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3