| Project/Area Number |
18592235
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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 |
Orthodontic/Pediatric dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
TANAKA Eiji Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (40273693)
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| Co-Investigator(Kenkyū-buntansha) |
TANNE Kazuo Hiroshima University, Graduate School of Biomedical Sciences, Professor (30159032)
WATANABE Mineo Hiroshima University, Graduate School of Biomedical Sciences, Assistant Professor (80325183)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Neuropathic pain / Cytokine / Pain transmission / Behavior test / Infraorbital nerve |
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| Research Abstract |
The current literature strongly implicates a role for proinflammatory cytokines such as interleukin (IL)-1 β and tumor necrosis factor-α in the genesis or maintenance of hyperalgesia. The cytokine cascade has emerged as an important contributor to the development of persistent pain states. Importantly, the involvement of cytokines in persistent pain does not appear to be limited to peripheral sensitization. Independent of release of cytokines from the periphery site of injury, inflammatory cytokines are induced in the central nerve system (CNS). IL-1 β is a prototype proinflammatory cytokine that is highly inducible in the CNS after injury. By acting on IL-1 receptors (IL-1R) that are present on neurons and glia, IL-1 β can activate distinct intracellular signaling pathways and influence cellular function. It has been shown that IL-1 β interacts with N-methyl-D-aspartate (NMDA) receptors through activation of Src family protein tyrosine kinases, leading to enhanced NMDA receptor function. The present study directly addresses the role of proinflammatory cytokines in orofacial pain mechanisms following the chronic constriction injury (CCI) of the infraorbital nerve (IN). We demonstrate that IL-1 beta is selectively activated in astroglia in the spinal trigeminal nucleus including the subnuclei interpolaris/caudalis (Vi/Vc) transition zone and caudal subnucleus caudalis (Vc), two important regions for processing of orofacial noxious input.
In conclusion, CCI of IN induced a upregulation of IL-1 beta in the spinal trigeminal nucleus including the laminated Vc and Vi/Vc. Mechanical hyperalgesia and allodynia at orofacial region developed after the chronic constriction injury of infraorbital nerve. The upregulated IL-1 beta was selectively colocalized with GFAP, a marker for astrocytes. Intrathecal infusion of IL-1ra, the naturally occurring antagonist of IL-1R, prevented the development of hyperalgesia/allodynia in orofacial region.
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