title: Regional osteoporosis due to osteoclast activation as a trigger for the pain-like behaviors in tail-suspended mice.
abstract: Pathological conditions with refractory skeletal pain are often characterized by regional osteoporotic changes such as transient osteoporosis of the hip, regional migratory osteoporosis, or complex regional pain syndrome (CRPS). Our previous study demonstrated that the acidic microenvironment created by osteoclast activation under high bone turnover conditions induced pain-like behaviors in ovariectomized mice through the stimulation of acid-sensing nociceptors. The aim of the present study was to examine whether regional transient osteoporotic changes are related to pain-like behaviors in the hind limb using tail-suspended model mice. The hind limbs of tail-suspended mice were unloaded for 2 weeks, during which time the mice revealed significant regional osteoporotic changes in their hind limbs accompanied by osteoclast activation. In addition, these changes were significantly recovered by the resumption of weight bearing on the hind limbs for 4 weeks. Consistent with the pathological changes in the hind limbs, pain-like behaviors in the mice were induced by tail suspension and recovered by the resumption of weight bearing. Moreover, treatment with bisphosphonate significantly prevented the triggering of the regional osteoporosis and pain-like behaviors, and antagonists of the acid-sensing nociceptors, such as transient receptor potential channel vanilloid subfamily member 1 and acid-sensing ion channels, significantly improved the pain-like behaviors in the tail-suspended mice. We, therefore, believe that regional transient osteoporosis due to osteoclast activation might be a trigger for the pain-like behaviors in tail-suspended model mice. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1226-1236, 2017.
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Dohke
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Iba
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Hanaka
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kanaya
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.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Okazaki
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D062646:Acid Sensing Ion Channel Blockers; D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002934:Cinnamates / Q000494:pharmacology / Q000627:therapeutic use; D003064:Cnidarian Venoms / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006614:Hindlimb / Q000502:physiology; D019417:Hindlimb Suspension; D008297:Male; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000150:complications*; D010146:Pain / Q000188:drug therapy / Q000209:etiology*; D059408:Pain Management; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D016474:Weight-Bearing
chemical_list: C501880:APETx2 protein, Anthopleura elegantissima; D062646:Acid Sensing Ion Channel Blockers; D000813:Anilides; D002934:Cinnamates; D003064:Cnidarian Venoms; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D050916:TRPV Cation Channels
keywords: pain-like behavior; regional osteoporosis; tail-suspended mouse