| Project/Area Number |
16K20430
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional basic dentistry
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 神経障害性疼痛 / 骨粗鬆症 / NK1受容体遮断薬 / NK１遮断薬 / 三環系抗うつ薬 / 鎮痛補助薬 / NK1受容体アンタゴニスト / 薬理学 / 生理学 / 神経科学 |
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| Outline of Final Research Achievements |
The aim of the present study was to reveal the mechanism of osteoporosis induced by neuropathic pain and to provide a molecular basis for a therapeutic approach in neuropathic pain patients accompanied by osteoporosis. The results in this study demonstrated that partial sciatic nerve ligation induced mechanical hypersensitivity and bone loss. Although there was a significant correlation between these symptoms, they were likely to be independent phenomena. Chronic treatment with pregabalin, an analgesic frequently used for neuropathic pain, attenuated the neuropathic pain, but not the bone loss, while netupitant, an inhibitor of NK1 substance P(SP) receptor, remedied both the neuropathic pain and bone loss in PSNL mice. These results suggest that hyperactivity of SP-containing sensory nerves is involved in both the mechanical hypersensitivity and bone loss induced by partial sciatic nerve ligation. NK1 receptors can be a therapeutic target for neuropathic pain accompanied by osteopenia.
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| Academic Significance and Societal Importance of the Research Achievements |
神経障害性疼痛は神経の傷害あるいは機能障害を原因とする慢性疼痛の一種であり、従来の鎮痛薬が著効しないことから、難治性であり、新たな治療法の開発が望まれている。また、神経障害性疼痛患者においては痛みだけではなく、骨密度の低下が起こることが報告されている。本研究では神経障害性疼痛モデルマウスにおいて機械痛覚過敏および骨量減少が見られ、独立した症状であり、それぞれに治療が必要である事を示した。また骨量減少にペプチド作動性知覚神経の異常興奮が関与し、NK1受容体遮断薬が、痛覚過敏と骨量減少を共に緩和することから、骨粗鬆症を伴う神経障害性疼痛の新たな治療ターゲットとなる可能性を示した。
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