2017 Fiscal Year Final Research Report
Therapeutic potential of the metabolic relationship between the product of two genetic markers for pain (gch1 and mthfr)
| Project/Area Number |
15K10556
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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 | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
林 維光 滋賀医科大学, 医学部, 助教 (80242973)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | GTP cyclohydrolase 1 / sensory neurons / tetrahydrobiopterin / pain / serotonin |
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| Outline of Final Research Achievements |
Tetrahydrobiopterin (BH4) is a cofactor required for the biosynthesis of neurotransmitters involved in the nociceptive neurotransmission. BH4 de novo synthesis is led by GTP cyclohydrolase 1 (GCH1) which is the first and rate-limiting enzyme in that synthetic pathway. In the other hand, BH4 salvage pathway is linked to the folate metabolic pathway via methyltetrahydrofolate reductase. Since GCH1, MTHFR are known as pain marker and availability in BH4 is linked to chronic pain, we evaluate the potential of those metabolic pathways in pain. Several approaches were used to leverage BH4 availability in vitro. The involvement of these metabolic pathways was assessed in animal model of visceral pain. Evolutional conservation of these metabolic pathways were assessed in higher invertebrate animal model. Our observation suggested that those pathways are conserved among species and involved in availability of BH4 in pain. However their modulation using drugs is facing specificity challenges.
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| Free Research Field |
麻酔・蘓生学
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