Critical roles of the chromogranin A-cathepsin B system in a transition of acute pain to a chronic pain state
| Project/Area Number |
24390416
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKE Hiro 九州大学, 歯学研究院, 准教授 (10420598)
HAYASHI Yoshinori 九州大学, 歯学研究院, 助教 (80582717)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | ミクログリア / カテプシンB / カテプシンS / クロモグラニンA / 炎症性疼痛 / 神経障害性疼痛 / 慢性疼痛 / モルヒネ / オートファジー / T細胞 / IFN-γ / IL-1β / カスパーゼ-1 / NF-κB / IL-18 |
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| Outline of Final Research Achievements |
In this study, we found that cathepsin B is an essential enzyme for the induction of chronic inflammatory pain through its activation of pro-caspase-1, which subsequently induces the maturation and secretion of IL-1β and IL-18 by spinal microglia. On the other hand, we found a peripheral pivotal role of cathepsin S in the development of neuropathic pain through the antigen-specific activation of CD4+ T-cells. After activation, CD4+ T-cells infiltrate into the dorsal spinal cord and secrete IFN-γ to reactivate microglia, which contribute to the transition of acute pain to a chronic pain state. Therefore, specific inhibitors for cathepsin B and cathepsin S may represent a useful new strategy for treating chronic pain.
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Report
(4 results)
Research Products
(37 results)
