The targeting treatment for prevention and restoration in patients with neuro-degenerative disease
| Project/Area Number |
20592374
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Yamaguchi University |
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Principal Investigator |
ISHIKAWA Toshizo Yamaguchi University, 大学院・医学系研究科, 教授 (90034991)
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| Co-Investigator(Kenkyū-buntansha) |
FURUKAWA Syoei 岐阜薬科大学, 薬学部, 教授 (90159129)
NAKANISHI Osamu 九州歯科大学, 歯学部, 教授 (50137345)
IBUKI Takae 京都府立医科大学, 医学系研究科, 講師 (90232587)
YAMAMOTO Misa 山口大学, 大学院・医学系研究科, 助教 (70379957)
MATSUMOTO Yoshihiro 山口大学, 大学院・医学系研究科, 学術研究員 (30364152)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 神経障害性疼痛 / 神経-グリア / 神経栄養因子 / シナプス再構築 / MAPキナーゼ / 慢性疼痛 / 脊髄可塑性 / グリア応答 / 磁気刺激治療 / 肝細胞 / 神経因性疼痛 / 神経可塑性 / p38-MAPK / 4-methylcathechol / magnetic field stimulation |
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| Research Abstract |
The neuro-glia activation in the spinal cord may mediate neuropathic pain. However, little is known about the roles of brain-derived neurotrophic factor (BDNF) and mitogen-activated protein kinase (MAPKs) in chronic pain. Although it is well documented that MAPK pathways can increase pain sensitivity via peripheral mechanisms, the present study focused on central mechanisms of MAPKs, especially ERK. In the present study, we characterized neuro-glia and evaluated pERK and c-FOS immunoreactivity after administration of 4-methylcatechol (4-MC), a BDNF inducer, can modify these derangements in relation to chronic pain. A chronic constriction injury (CCI) model as for neuropathic pain model was prepared in SD rats and pain was assessed by a reduction in paw withdrawal latency (PWL) to heat stimuli. 4-MC was injected chronically after CCI. On day 14, k252a (Trk-B receptor inhibitor) or SP600125 (JNK-1 inhibitor) was injected to determine if the analgesic effects of 4-MC could be reversed. The animals were perfused with 4% paraformaldehyde followed by fixation for immunohistochemistry (c-FOS, pERK). The rats showed a persistent decrease in PWL after CCI. On day 14, there was increase in pERK and c-FOS in regions related to pain pathways and regions associated with emotion. 4-MC reduced the decrease in PWL and this effect was reversed by k252a and SP600125, but not by minocyclin, microglial inactivator.
These results suggest that the derangement of neuro-glia associated with pERK in pain-emotion system are responsible for chronic pain Neurotrophic factor related compound ameliorates chronic pain by preventing abnormal intracellular signaling via induction of BDNF and normalization of cell responses.
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Report
(4 results)
Research Products
(63 results)
