| Project/Area Number |
23790646
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pain science
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| Research Institution | Nagoya City University |
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Principal Investigator |
OHSAWA Masahiro 名古屋市立大学, 大学院・薬学研究科, 准教授 (80369173)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 慢性疼痛 / 帯状回皮質 / ミクログリア / 神経障害 / ミノサイクリン / アストロサイト / 視床 / グリア細胞 / 神経伝達 / グルタミン酸 / gabapentin |
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| Research Abstract |
Neuropathic pain that results from the nerve injury is the chronic pain that is hard to treat with analgesics. The present study was designed to reveal the supraspinal mechanisms of neuropathic pain using partial sciatic nerve-ligated mouse model. The mechanical hyperalgesia in nerve-ligated mice were reversed by the preemptive, but not postinjury, administration of L-type calcium channel α2δsubunit blocker gabapentin. It is suggested that centrally administered gabapentin attenuates the development, but not maintenance of neuropathic pain. In the next, we examined the expression of neuronal cells in several brain regions. We observed that the expressions of Iba-1 that is a marker of microglia and GFAP that is a marker of astrocyte were increased in the anterior cingulate cortex (ACC). Intra-ACC treatment with microglial inhibitor minocycline attenuated the hyperalgesia in nerve-ligated mice, suggesting that the activation of microglia in the ACC is involved in the expression of hyperalgesia in neuropathic pain. Moreover, inhibition of the ACC microglia also attenuate the activation of astrocytes. Furthermore, the increased phosphorylation of AMPA receptor subunit GluA1 at ser831 in nerve-ligation is attenuated by the intra-ACC treatment with minocycline. Therefore, it is possible that the ACC microglial activation in nerve-ligation is involved in the neuropathic pain, which is mediated by the enhanced glutamatergic function.
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