Role of spinal LPCAT2, an inducible PAF synthesis enzyme on development and maintenance of painful peripheral neuropathy models in mice
| Project/Area Number |
16K11550
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Conservative dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
MOTOYAMA NAOYO 広島大学, 医歯薬保健学研究科(歯), 助教 (70509661)
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| Co-Investigator(Kenkyū-buntansha) |
土肥 敏博 広島文化学園大学, 看護学部, 教授 (00034182)
峯岡 茜 広島大学, 病院(歯), 助教 (00452623)
森田 克也 広島文化学園大学, 看護学部, 教授 (10116684)
北山 友也 武庫川女子大学, 薬学部, 講師 (60363082)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 血小板活性化因子（PAF） / PAF合成酵素（LPCAT2） / 疼痛の発症と維持 / LPCAT2阻害薬 / 鎮痛薬開発 / PAF合成酵素 / 鎮痛 / PAF / 歯学 / 疼痛 / LPCAT2 / 血小板活性化因子(PAF) |
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| Outline of Final Research Achievements |
The present study examined the pain relieving effect of knockdown of spinal LPCAT2, a novel inducible PAF synthesis enzyme on several neuropathic pain models. The amount of a LPCAT2 protein significantly increased in the spinal cord after nerve ligation and bone cancer pain model in animal. The knockdown of LPCAT2 and PAF receptor ameliorated tactile allodynia. Knockdown of LPCAT2 and PAF receptor before nerve injury prevented the development of pain. The appearance of pain behaviors was abolished by consecutive administration of TCV-309, a specific PAF receptor antagonist. The anti-nociceptive effects of knockdown of LPCAT2 and PAF receptor, and administration of TCV-309 was appeared certainly in any other models tested.
These data suggest that spinal LPCAT2 play a causal role in the development and maintenance of neuropathic pain in animal models, and that LPCAT2 antagonists may highlight a potential novel therapeutic strategy for the treatment of persistent neuropathic pain.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により創薬が実現化すると種々の難治性疼痛性疾患治療の『恒久的な緩和治療』や『先行除痛』，『痛みの記憶回避』への道が開ける可能性がある，さらには健康長寿（『社会への参画』）の実現に大きく寄与する．それは，痛みの克服，さらには活力ある高齢社会，先制医療の実現をもたらす包括的研究としても意義が高く，医学的，社会的貢献度は非常に高いものがある．
加えて，PAFが関係する病態の治療薬となる可能性もあり，医薬品としての開発も期待が大きい．がん生存率の延伸やがんの化学療法に伴う神経障害性疼痛に対しても有効性を認めており，がんの薬物療法においても福音をもたらす可能性も期待される．
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Report
(3 results)
Research Products
(6 results)
