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In addition, bisphosphonate and the antagonist of transient receptor potential vanilloid type 1 (TRPV1), an acid\u2010sensing nociceptor, improved the threshold value of pain\u2010like 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<jats:sup>+<\/jats:sup>\u2010ATPase, known as an proton pump, (ii) an antagonist of acid\u2010sensing ion channel (ASIC) 3, as another acid\u2010sensing nociceptor, and (iii) the P2X2\/3 receptor, as an ATP\u2010ligand nociceptor, on pain\u2010like behavior in OVX mice. This inhibitor and antagonists were found to improve the threshold value of pain\u2010like 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. \u00a9 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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