title: P2X7 receptor-deficient mice are susceptible to bone cancer pain.
abstract: The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a separate pain state compared with those of neuropathic and inflammatory pain. However, the recent discovery of a P2X7 receptor splice variant expressed in the knockout mice used for this study complicates the interpretation of the results. The P2X7 splice variant receptor was detected in the spinal cord but not in osteoclasts of the P2X7R KO mouse. Further experiments are needed to elucidate the exact role of the P2X7 receptors in bone cancer pain.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, Copenhagen University, Copenhagen, Denmark Center for Ageing and Osteoporosis, Research Centre Glostrup, Glostrup Hospital, Denmark Odense University Hospital, University of Southern Denmark, Odense, Denmark Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Rikke Rie
authors.initials: RR
authors.lastname: Hansen
authors.forename: Christian K
authors.initials: CK
authors.lastname: Nielsen
authors.forename: Arafat
authors.initials: A
authors.lastname: Nasser
authors.forename: Stine I M
authors.initials: SIM
authors.lastname: Thomsen
authors.forename: Laura F
authors.initials: LF
authors.lastname: Eghorn
authors.forename: Yen
authors.initials: Y
authors.lastname: Pham
authors.forename: Cecilia
authors.initials: C
authors.lastname: Schulenburg
authors.forename: Susanne
authors.initials: S
authors.lastname: Syberg
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Stanko S
authors.initials: SS
authors.lastname: Stojilkovic
authors.forename: Niklas R
authors.initials: NR
authors.lastname: Jorgensen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Heegaard
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D045744:Cell Line, Tumor; D004274:DNA, Recombinant / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012516:Osteosarcoma / Q000150:complications*; D010146:Pain / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics*; D010147:Pain Measurement / Q000379:methods; D058920:Purinergic P2X Receptor Antagonists / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D058486:Receptors, Purinergic P2X7 / Q000172:deficiency* / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism; D013777:Tetrazoles / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: C523668:3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine; D004274:DNA, Recombinant; D005904:Glial Fibrillary Acidic Protein; D058920:Purinergic P2X Receptor Antagonists; D011725:Pyridines; D058486:Receptors, Purinergic P2X7; D013777:Tetrazoles