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Acid‐sensing ion channel 3 or P2X2/3 is involved in the pain‐like behavior under a high bone turnover state in ovariectomized mice
Author(s) -
Kanaya Kumiko,
Iba Kousuke,
Abe Yasuhisa,
Dohke Takayuki,
Okazaki Shunichiro,
Matsumura Tadaki,
Yamashita Toshihiko
Publication year - 2016
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.23047
Subject(s) - ovariectomized rat , acid sensing ion channel , osteoclast , nociceptor , trpv1 , chemistry , endocrinology , medicine , bone resorption , bone remodeling , bisphosphonate , antagonist , transient receptor potential channel , osteoporosis , receptor , ion channel , nociception , estrogen
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. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:566–573, 2016.