The mechanism of neuron pathic pain analyzed by DNA microarray.
| Project/Area Number |
15390473
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Osaka University |
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Principal Investigator |
HAGIHIRA Satoshi (2005) Osaka University, Hospital, Assistant professor, 医学部附属病院, 講師 (90243229)
内田 一郎 (2003-2004) 大阪大学, 医学系研究科, 助教授 (00232843)
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| Co-Investigator(Kenkyū-buntansha) |
MASHIMO Takashi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (60157188)
NAKAE Aya Osaka University, Graduate School of Medicine, Instructor, 医学系研究科, 助手 (60379170)
INOUE Takaya Osaka University, Graduate School of Medicine, Endowed Chair Instructor, 医学系研究科, 寄附講座助手 (00335358)
柴田 政彦 大阪大学, 医学系研究科, 助手 (50216016)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | Chronic pain / Spinal injury / Inhibitory transmission / GABA / Synapse / Tonic inhibition / Plastisity / Animal model / 神経因性疼痛 / 遺伝子 / DNAマイクロアレイ / 脊髄損傷モデル / GABA_A受容体 / パッチクランプ法 / ラット / rt-PCR法 / マイクロアレイ / 疼痛モデル / mRNA / cDNA / クローン / マウス / DNAマイクロアレー / 脊髄 / パッチクランプ / 神経可塑性 / 電気生理 |
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| Research Abstract |
Neuropathic pain is a common complication after spinal cord injury (SCI) and uncontrolled pain severely compromises the quality of life. As in other forms of chronic neuropathic pain, standard pharmacotherapy fails to adequately control post-SCI pain and a new mechanism-based pain therapy is needed. We here discovered that tonic inhibition mediated by GABAA exist in the spinal cord and that SCI attenuates the tonic inhibition. This discovery led us to our working hypothesis that attenuated tonic inhibition in the spinal cord mediates hyperexcitability and the development of neuropathic pain. The presence of tonic inhibitory receptors always open in low ambient concentration of GABA at the extrasynaptic region was recently established in the brain, however, little information exists on the role of tonic inhibition in the spinal cord. Our proposal is a comprehensive study of the tonic inhibition in the spinal cord. We start with a molecular biological study identifying the subunits comprising the GABAergic receptors mediating tonic inhibition in the second order sensory neurons in substantia gelatinosa. Next we study the pathophysiological role of tonic inhibition in neuropathic pain after SCI using a well-characterized rat spinal contusion model. Finally a recombinant lentivirus mediated "gene-therapy" for post-SCI pain targeting tonic inhibition in the spinal cord will be examined. This project revealed the role of spinal tonic inhibition in normal and injured spinal cord and contribute towards the development of a mechanism-based therapy for post-SCI neuropathic pain.
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Report
(4 results)
Research Products
(17 results)
