Elucidation for a mechanism of skeletal pain induction related to expression changes of bone metabolic markers and pain-related molecules in osteoporosis
Project/Area Number |
26462308
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | Sapporo Medical University |
Principal Investigator |
iba kousuke 札幌医科大学, 医学部, 准教授 (60363686)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | 疼痛 / 骨粗鬆症 / 骨代謝亢進 / 破骨細胞 / ビスホスホネート / 侵害受容体 / 炎症性サイトカイン / 拮抗薬 / 尾部吊り下げモデル / 局所性骨粗鬆化 / 疼痛行動 / 酸性環境 / 再荷重 / TRPV1 / ASIC / P2X / 骨代謝マーカー |
Outline of Final Research Achievements |
We demonstrated that antagonists to TRPV1, ASIC and P2X2 improved the threshold value of pain-like behavior in OVX mice. These results suggest that the activation of these nociceptors by pathological conditions as acidic environment resulting from osteoclast activation cause skeletal pain in osteoporosis. We also demonstrated that an array of nociceptors, TRPV1, ASIC and P2X2/3, were simultaneously expressed in bone tissue under a high bone turnover state in OVX mice. In addition, the pain-like behaviors in tail-suspended mice were significantly increased in comparison with those in control mice. These mice showed regional osteoporotic changes in the hind limbs accompanied by an increase in bone resorption due to osteoclast activation. The pain-like behaviors accompanying the regional osteoporotic changes were significantly improved by the resumption of weight bearing, or treatment with bisphosphonate or acid-sensing nociceptor antagonists.
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Report
(4 results)
Research Products
(16 results)