| Project/Area Number |
16591543
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
MIZOBUCHI Satoshi Okayama University, Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (70311800)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Masataka Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (20158380)
TAKAHASHI Toru Okayama University, Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (40252952)
NAKATSUKA Hideki Okayama University, Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (70263580)
NINOMIYA Yoshifumi Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (70126241)
MORITA Kiyoshi Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (40108171)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | molecular mechanisms / acute pain / chronic pain / BDNF / spinal cord / 疼痛メカニズム / 難治性疼痛 / 遺伝子治療 |
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| Research Abstract |
To investigate molecular mechanisms of acute and chronic pain, we achieved two main projects in 2004-2005. First, to clarify the influence of acute pain under chronic neuropathic pain states, we examined the expression of brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP) in the spinal cord of rats with L5 spinal nerve ligation (SNL)-induced neuropathy and investigated the expression of c-Fos in the spinal cord after injection of formalin in the hindpaw of rats with SNL. Four weeks after SNL, the withdrawal threshold was significantly lower in the SNL group. In the SNL group, expression of BDNF in the L4 and L5 superficial dorsal horn was significantly decreased compared to that in the sham group. CGRP protein in the L5 but not in the L4 dorsal horn was significantly decreased compared to that in the sham group. After formalin injection, spontaneous pain responses in the SNL group were significantly decreased. Immunolabeling for c-Fos was significantly
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decreased in the L4 and L5 dorsal horn in the SNL. In this study, these results indicate that decreased neuronal activity in the spinal cord in response to inflammatory pain may be important for altering the perception of acute pain and decreased BDNF expression in response to SNL-induced neuropathy may be involved in this alteration. Second, we assessed multiple BDNF transcripts semiquantitatively by reverse transcription polymerase chain reaction (RT-PCR) technique using exon-specific primers because BDNF is one of the most noteworthy substances in pain research. In naive rats, there was no significant difference between in ipsilateral and contralateral dosal root ganglions(DRGs) as for any exons expression. In L5SNL rats, exon V expression elevated significantly in ipsilateral L4DRG compared to contralateral, which demonstrates increased expression of total BDNF mRNA. In ipsilateral side, a significant increase in exon I expression was observed. In L5 DRGs of L5SNL rats, there was no significant difference in exon V expression. Among four 5' exons, only the ipsilateral exon I expression elevated significantly compared to contralateral. Our results showed that most of BDNF mRNA elevated in ipsilateral L4 DRG of L5SNL model is exon I mRNA. This indicates that exon I mRNA plays important role in modulating neuronal transmission in neuropathic pain. Less
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