title: Inhibitory effect of bisphosphonate on osteoclast function contributes to improved skeletal pain in ovariectomized mice.
abstract: The aim of this study was to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of bisphosphonate (BP) on pain in an ovariectomized (OVX) mouse model. We evaluated skeletal pain in OVX mice through an examination of pain-like behavior as well as immunohistochemical findings. In addition, we assessed the effects of alendronate (ALN), a potent osteoclast inhibitor, on those parameters. The OVX mice showed a decrease in the pain threshold value, and an increase in the number of c-Fos immunoreactive neurons in laminae I-II of the dorsal horn of the spinal cord. Alendronate caused an increase in the pain threshold value and inhibited c-Fos expression. The serum level of tartrate-resistant acid phosphatase 5b, a marker of osteoclast activity, was significantly negatively correlated with the pain threshold value. Furthermore, we found that an antagonist of the transient receptor potential channel vanilloid subfamily member 1, which is an acid-sensing nociceptor, improved pain-like behavior in OVX mice. These results indicated that the inhibitory effect of BP on osteoclast function might contribute to an improvement in skeletal pain in osteoporosis patients.
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Abe
authors.forename: Kousuke
authors.initials: K
authors.lastname: Iba
authors.forename: Koichi
authors.initials: K
authors.lastname: Sasaki
authors.forename: Hironori
authors.initials: H
authors.lastname: Chiba
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kanaya
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawamata
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
authors.forename: Muneteru
authors.initials: M
authors.lastname: Sasaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D019386:Alendronate / Q000494:pharmacology; D000818:Animals; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D050051:Transient Receptor Potential Channels / Q000378:metabolism
chemical_list: D004164:Diphosphonates; D007527:Isoenzymes; D016760:Proto-Oncogene Proteins c-fos; D050051:Transient Receptor Potential Channels; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019386:Alendronate