Clarification of mechanisms of sciatica due to disc herniation and development of new treatment
| Project/Area Number |
16591502
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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 |
Orthopaedic surgery
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| Research Institution | Fukushima Medical University School of Medicine |
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Principal Investigator |
YABUKI Shoji Fukushima Medical University, Orthopaedic Surgery, Assistant professor, 医学部, 講師 (00260779)
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| Co-Investigator(Kenkyū-buntansha) |
KIKUCHI Shin-ichi Fukushima Medical University, Orthopaedic Surgery, Professor, 医学部, 教授 (80045773)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | neuroscience / brain / nerve / disc herniation / sciatica / nerve root involvement |
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| Research Abstract |
1)Changes of nerve growth factor(NGF) in the dorsal root ganglia(DRG) and pain-related behavior were examined using a rat model of disc herniation. The animals had their left L4 nerve roots and associated DRG exposed and were equally divided into 4 groups : L4-5 disc puncture, displacement of L4 nerve roots/DRG, the combination of disc puncture and displacement, and sham exposure. In the combination model, there were more pronounced changes in NGF induction and both mechanical and thermal threshold during 7 days after surgery compared to other groups. These data suggest the possibilities that elevated NGF level partly involved in pain behavior and further the combined model mimicking the clinical situation is helpful to advance the understanding of the mechanisms underlying sciatica due to lumbar disc herniation.
2)Changes of brain-derived neurotrophic factor(BDNF), as a modulator of pain, was examined using experimental disc herniation model at DRG and spinal cord. Application of nucleus pulposus induced a marked increase of BDNF immunoreactivity in number in the DRG neurons and within the superficial layer in the dorsal horn compared with the sham group (p<0.01).
3)Based on the results of 2) experiment, effects of Infliximab, an anti-TNF-alpha antibody, was examined using the same model. Infliximab treatment reduced the BDNF induction in both DRG and spinal cord (p<0.05). These findings indicate that Infliximab attenuates the elevated BDNF levels induced by nucleus pulposus. The present study therefore further indicates the importance of TNF-alpha in sciatica due to disc herniation and the possible therapeutic use of a TNF-alpha inhibitor for this condition.
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Report
(3 results)
Research Products
(7 results)
