2022 Fiscal Year Final Research Report
The role of anterior cingulate cortical microglia in pathophysiology of neuropathic pain and novel drug targets
| Project/Area Number |
20K07291
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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 48030:Pharmacology-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
森岡 徳光 広島大学, 医系科学研究科(薬), 教授 (20346505)
中村 庸輝 広島大学, 医系科学研究科(薬), 助教 (60711786)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ミクログリア / 神経障害性疼痛 |
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| Outline of Final Research Achievements |
In this study, we are intended to elucidate the role of microglia in pathophysiology of neuropathic pain by using partial sciatic nerve ligation (PSNL) model mice. Inhibition of microglia activation by minocycline, local hippocampal microglia depletion with clodronate liposome, or inhibition of high mobility group box-1 (HMGB1) by GZA and anti-HMGB1 antibody blocked cognitive impairment induced by PSNL. Cognitive impairment could be due to degenerative changes in contralateral hippocampal neurons, as observed in PSNL mice. Treatment with anti-HMGB1 antibody blocked PSNL-induced degenerative effects observed in hippocampal neurons. Thus, HMGB1-mediated microglial activation and changes neuronal plasticity could be related to cognitive impairment associated with neuropathic pain.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
慢性疼痛が如何にして脳ミクログリアを活性化するのかは、これまで全く不明であったが、本研究はミクログリア活性化に対するHMGB1の関与を明らかにした。これらの独自の知見を切り口として、慢性疼痛時に活性化する脳ミクログリアの機能と役割について見出すことが出来れば、鎮痛薬の創薬ターゲットとしてのミクログリアの新たな可能性を創造することができる。
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