Elucidation of the mechanisms of cellar and molecular transduction to the brain for trigger of pain chronification
Project/Area Number |
15H04968
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Anesthesiology
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Research Institution | Osaka University |
Principal Investigator |
NAKAE Aya 大阪大学, 生命機能研究科, 特任教授(常勤) (60379170)
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Co-Investigator(Kenkyū-buntansha) |
熊谷 雄太郎 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (00528408)
中井 國博 福井大学, 学術研究院医学系部門(附属病院部), 准教授 (80362705)
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Research Collaborator |
YOSHIOKA yoshichika
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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Keywords | マクロファージ / 痛み / 術後遷延痛 / 高解像MRI / 疼痛モデル / 高解像MRI / 遷延性疼痛 / 免疫 / イメージング |
Outline of Final Research Achievements |
We developed a postoperative persistent pain model, and analyzed the variation of cytokines according to the time course. The expression patterns in KO mice with diminished pain related behavior were remarkably different from those of WT. Changes in the brain activity evaluated using Manganese-Enhanced MRI(MEMRI) in the pain model showed no significant difference in the enhanced level at each region between naïve, acute and chronic stages. However, their patterns of co-enhanced level were significantly different from those before the surgery in both acute and chronic stages. We evaluated the brain activity by MEMRI using animals that showed significant higher thresholds of mechanical stimulation after administration of analgesics. Brain activity patterns showed that buprenorphine-administered animals displayed resemble pattern of pre-surgery animals. We also confirmed dose dependent patterns when comparing to naïve, low-dose and high-dose gabapentin-administered animals.
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Academic Significance and Societal Importance of the Research Achievements |
「痛み」はヒトの持つ感覚の中でとりわけ不快な感覚であり、特に痛みによる経済損失はガンや心臓病より大きく、最優先で取り組むべき課題である。慢性痛に伴う脳内のネットワーク異常が痛みのメカニズムとして着目されているが、それが原因であるのか結果であるのかの議論はなされておらず、脳のネットワーク異常が起こる仕組みも解明されていない。 本研究では、炎症性疼痛モデルを作成し、マクロファージから放出される液性因子とマクロファージそのものの脳への迷入と脳内ネットワークの変化の関係を明らかにし、高解像MRIで脳内活動パターンを解析することで、痛みの慢性化のきっかけとなる脳への細胞・分子伝達メカニズムを解明した。
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Report
(5 results)
Research Products
(13 results)
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[Presentation] Data Driven Quantification of the Effects of different doses of Gabapentin for Pain in Chronic Phase in Mice using Manganese-Enhanced MRI with AI based analyses2019
Author(s)
Aya Nakae, Kunihiro Nakai, Yoshichika Yoshioka, Hiroki Kato, Chie Kishimoto, Koutaro Nomura, Miho Nakanishi, Makoto Miyamae, Ryotaro Urabe, Junichiro Enmi, Toshio Yanagida
Organizer
European Pain Federation
Related Report
Int'l Joint Research
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[Presentation] マウスの慢性の痛みのAIを用いた客観的評価の試み~マンガン造影MRIを用いた投薬量による違いの検証~2019
Author(s)
岸本千恵, 中江文, 中井國博, 吉岡芳親, 加藤弘樹, 能村幸大郎, 中西美保, 宮前誠, 浦邊亮太朗, 圓見純一郎, 柳田敏雄
Organizer
第41回日本疼痛学会
Related Report
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