| Project/Area Number |
18K09087
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
OHNISHI Hideo 産業医科大学, 医学部, 非常勤医師 (20279342)
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| Co-Investigator(Kenkyū-buntansha) |
上田 陽一 産業医科大学, 医学部, 教授 (10232745)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | TRPV1 / 神経障害性疼痛 / 坐骨神経部分結紮 / 視床下部 / 脊髄後角 / TRPV１ / TRPV4 / オキシトシン / 侵害受容調節 |
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| Outline of Final Research Achievements |
We analyzed mechanical/heat sensitivities and glial/neuronal activities in laminae I and II in the spinal dorsal horn by employing partial sciatic nerve ligation (pSNL) using TRPV1 knockout (Trpv1-/-) mice. Mechanical/heat sensitivities, expression levels of microglial Iba-1 and astrocytic GFAP, and the number of FosB-positive neurons were significantly increased on days 7 and 14 in the pSNL group of both wild type (WT) and Trpv1-/- mice. The number of FosB/OXT double positive neurons in the hypothalamus were few in both WT and TRPV1-/-. While mechanical sensitivity was comparable between WT and Trpv1-/- mice, the threshold against heat sensitivity was markedly prolonged in Trpv1-/- than WT mice on day 14 after pSNL. Conversely, the increment of FosB-positive neurons was significantly attenuated in Trpv1-/- than WT mice on days 7 and 14 after pSNL. These results suggest that TRPV1 may modulate thermal perception via increased astrocytes in the dorsal horn.
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| Academic Significance and Societal Importance of the Research Achievements |
神経障害性疼痛の病態は複雑であり、難治性である。TRPチャネルの中枢神経系や脊髄における役割は不明な点が多い。TRPチャネルの一つであるTRPV1に着目し、TRPV1 KOマウスを用いてTRPV1が神経障害性疼痛の熱痛覚過敏に関与していることを明らかにした。本研究課題では、アストロサイト阻害薬やTRPV１拮抗薬を投与すると神経障害性疼痛による痛覚過敏が改善することを証明したことにより、これらの薬剤が神経障害性疼痛の治療のターゲットとして注目される可能性があり、社会的意義があると考える。
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