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 1) an inhibitor of vacuolar H+ -ATPase, known as an proton pump, 2) an antagonist of acid-sensing ion channel (ASIC) 3, as another acid-sensing nociceptor, and 3) the P2 × 2/3 receptor, as an ATP-ligand nociceptor, on pain-like behavior in OVX mice.
