Acid-sensing ion channel 3 or P2X2/3 is involved in the pain-like behavior under a high bone turnover state in ovariectomized mice.
We have recently demonstrated that pathological changes leading to increased bone resorption by osteoclast activation are related to the induction of pain-like behavior in ovariectomized (OVX) mice. In addition, bisphosphonate and the antagonist of transient receptor potential vanilloid type 1 (TRPV1), an acid-sensing nociceptor, improved the threshold value of pain-like behaviors accompanying an improvement in the acidic environment in the bone tissue based on osteoclast inactivation. The aim of this study was to evaluate the effect of (i) an inhibitor of vacuolar H(+) -ATPase, known as an proton pump, (ii) an antagonist of acid-sensing ion channel (ASIC) 3, as another acid-sensing nociceptor, and (iii) the P2X2/3 receptor, as an ATP-ligand nociceptor, on pain-like behavior in OVX mice. This inhibitor and antagonists were found to improve the threshold value of pain-like behavior in OVX mice. These results indicated that the skeletal pain accompanying osteoporosis is possibly associated with the acidic microenvironment and increased ATP level caused by osteoclast activation under a high bone turnover state.
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Kumiko
K
Kanaya
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Kousuke
K
Iba
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Yasuhisa
Y
Abe
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Takayuki
T
Dohke
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Shunichiro
S
Okazaki
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tadaki
T
Matsumura
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Toshihiko
T
Yamashita
D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000813:Anilides; D000818:Animals; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism; D002227:Carbazoles; D059350:Chronic Pain / Q000209:etiology / Q000378:metabolism*; D002934:Cinnamates; D003064:Cnidarian Venoms; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018942:Macrolides; D051379:Mice; D059226:Nociceptive Pain / Q000209:etiology / Q000378:metabolism*; D010024:Osteoporosis / Q000150:complications*; D010052:Ovariectomy; D010636:Phenols; D011083:Polycyclic Compounds; D058469:Receptors, Purinergic P2X / Q000378:metabolism*
C470346:A-317491; C501880:APETx2 protein, Anthopleura elegantissima; C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D000813:Anilides; D002227:Carbazoles; D002934:Cinnamates; D003064:Cnidarian Venoms; D016207:Cytokines; D018942:Macrolides; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D010636:Phenols; D011083:Polycyclic Compounds; D058469:Receptors, Purinergic P2X; C040929:bafilomycin A1; C007005:carprofen
P2X2/3; acid-sensing ion channel (ASIC); osteoporosis; pain; vacuolar H+-ATPase