| Project/Area Number |
16K10987
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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 |
Anesthesiology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
藤原 淳 大阪医科大学, 医学部, 助教 (00773516)
森本 賢治 大阪医科大学, 医学部, 助教 (20388250)
上野 健史 大阪医科大学, 医学部, 助教 (70782283)
中尾 謙太 大阪医科大学, 医学部, 助教 (50815719)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | がん性疼痛 / 神経障害性疼痛 / 脊髄 / アクロメリン酸 / アストロサイト / ミクログリア / 乳酸脱水素酵素 / アロディニア / MMP / 神経障害性痛 / がん性痛 |
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| Outline of Final Research Achievements |
Neuropathic pain, resulting from peripheral nerve injury, is characterized by spontaneous and long-lasting pain, hyperalgesia, and allodynia. Peripheral nerve injury triggers long-term plastic changes along sensory pathways. Synaptic plasticity is a key mechanism for neuropathic pain. Bone cancer pain control is difficult because it includes various characteristics of pain such as nociceptic and neuropathic pain.
We investigated the effect of MMP-9 on cancer pain in mouse bone metastasis model. The pain behavior was significantly alleviated by MMP-9 inhibitor. MMP-9 expression was significantly elevated in the bone tissue in the early-phase and in the ipsilateral spinal cord in the late-phase.
Stiripentol, an effective antiepileptic drug, was recently shown to act as an inhibitor of lactate dehydrogenase in astrocytes. We demonstrated that stiripentol was effective against neuropathic pain and suggested that the astrocyte-neuron lactate shuttle was involved in such pain.
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| Academic Significance and Societal Importance of the Research Achievements |
がん性疼痛は、侵害受容性疼痛、神経障害性疼痛が混在し難治性であり約20%は薬剤に抵抗を示す。世界保健機構（WHO）では「がん性疼痛は治療できる症状であり、治療すべき症状である」と提言している。神経障害性疼痛やがん性疼痛の病態解明を進めることにより、薬剤抵抗性疼痛の根治療法確立に向け大きく前進する。
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