Central effects of blockades of inhibitory neurotransmitter transporters in neuropathic pain models.
| Project/Area Number |
16K10989
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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 | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原 幸治 産業医科大学, 大学病院, 准教授 (20331001)
佐多 竹良 産業医科大学, 名誉教授、学長等, 名誉教授 (60128030)
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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 | 神経障害性痛 / トランスポーター / 中枢作用 / 鎮痛作用 / 糖尿病モデル / 神経障害性疼痛 / 抗不安作用 / グリシン / GABA |
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| Outline of Final Research Achievements |
Central effects of blockades of inhibitory neurotransmitter transporters on hyperalgesia, anxiety, and depression were examined in rat neuropathic pain models. A selective glycine transporter 2 (GlyT2) inhibitor ALX1393 and a selective GABA transporter 3 (GAT3) inhibitor SNAP5114 were administered intracerebroventriculary. In chronic constriction injury (CCI) model and diabetic polyneuropathy model, ALX1393 inhibited cold and mechanical hyperalgesia. In contrast, SNAP5114 had no effect on the cold and mechanical hyperalgesia in both models. In the CCI model, a high dose of ALX1393 decreased total moving distance in the open field. Both ALX1393 and SNAP5114 had no effect on percentage of the time spent in the central area of the open field and time spent in the open arms of elevated plus maze. These results indicate that GlyT2 but not GAT3 in the brain modulates nociceptive transmission and that neither GlyT2 nor GAT3 is involved in anxiety and depression in the neuropathic pain models.
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| Academic Significance and Societal Importance of the Research Achievements |
有効性の高い神経障害性痛治療薬の開発が求められている。疼痛抑制機構の破綻が神経障害性痛の病態の一つであるため、これを賦活化させることが治療に有効である。脳内のグリシントランスポーター2 (GlyT2)の機能をGlyT2阻害薬で抑え、抑制性神経伝達物質グリシンの働きを強めたところ、ラットに発現させた機械及び冷痛覚過敏に対する鎮痛作用が現れた。一方、高用量のGlyT2阻害薬は自発運動を低下させた。研究結果からGlyT2は脳内で疼痛閾値の調節に関与していると考えられ、運動機能を低下させる副作用の懸念はあるものの、新しい神経障害性痛治療薬のターゲットとして期待される。
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Report
(4 results)
Research Products
(2 results)
