2003 Fiscal Year Final Research Report Summary
Gene therapy of pain by expressing endogenous opioid peptide
| Project/Area Number |
14571442
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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, Anesthesiology and Resuscitology, Assistant Professor, 医学部・歯学部附属病院, 講師 (70311800)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATSUKA Hideki Okayama University Hospital of Medicine and Dentistry, Anesthesiology and Resuscitology, Assistant Professor, 医学部・歯学部附属病院, 講師 (70263580)
TAKAHASHI Toru Okayama University Graduate School of Medicine and Dentistry, Anesthesiology and Resuscitology, Assistant Professor, 大学院・医歯学総合研究科, 助手 (40252952)
YOKOYAMA Masataka Okayama University Graduate School of Medicine and Dentistry, Anesthesiology and Resuscitology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (20158380)
NINOMIYA Yoshifumi Okayama University Graduate School of Medicine and Dentistry, Molecular biology and Biochemistry, Professor and Chairman, 大学院・医歯学総合研究科, 教授 (70126241)
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| Project Period (FY) |
2002 – 2003
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| Keywords | pain / Gene therapy / intractable pain / endogenous opioid peptide / pain mechanism |
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| Research Abstract |
For aiming at gene therapy of pain by expressing endogenous opioid peptide, we achieved three main projects in 2002-2003. First, to clarify the significance of fos expression in the spinal cord of rats after the formalin test, we investigated the time course and location changes of c-fos and FOS expression, by using Northern blotting and immunohistochemical technique. The behavior test showed typical two phases induced by the formalin test. The amount of c-fos increased at 0.5 h after the formalin injection and returned to control level at 6 h. Also, the expression of FOS increased at 0.5 h, and the increase continued more than 6 h. At the early phase, the upregulation of FOS occurred in the superficial layers(laminae I-II ), and later it occurred in the deep layers (laminae V-VI) of the dorsal horn. In this study, we demonstrate that the pain caused by formalin injection induces c-fos mRNA translated to FOS protein in the spinal cord neurons. And the location changes of FOS expression
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in the later phase would imply the change of the mechanism of the central sensitization on the formalin test. Second, we investigated the spatial and temporal patterns of Fos expression in the dorsal horn of the spinal cord caused by plantar master in the rat and the effects of pretreatment with local anesthetics(0.5% Bupivacaine, 2% lidocaine). Pain behavior and Fos expression in the L_4-L_5 spinal cord were assessed at 1, 3, 6, 24, 48, 72, and 120 h after the master. The withdrawal threshold to mechanical stimulation decreased significantly at 1 h until 120 h, and pretreatment with local anesthetics increased the threshold significantly at 1 h and 6 h in comparison to that in the saline group. In the saline group, Fos expression was detected predominantly in laminaes I-II and V-VI, and the total Fos expression was maximal at 1 h and then decreased gradually. Pretreatment with local anesthetics suppressed Fos expression significantly in all layers and this suppression continued for several days. This study provides evidence of spatial and temporal changes in Fos expression induced by plantar master. Furthermore, although pretreatment with local anesthetics suppresses Fos expression for several days in the postoperative period, the analgesic effect is observed only for the expected duration of the local anesthetic used. Third, we confirmed that GFP(green fluorescent protein) was produced in spinal cord cells by injection of adenovirus with GFP to rats. Less
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Research Products
(2 results)
