2004 Fiscal Year Final Research Report Summary
Therapy for intractable pain by intrathecal administration of antisense oligonucleotides of neurotrophic factor
Project/Area Number |
14571438
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Anesthesiology/Resuscitation studies
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Research Institution | Okayama University |
Principal Investigator |
YOKOYAMA Masataka Okayama University, Graduate School of Medicine, Dentistry, & Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20158380)
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Co-Investigator(Kenkyū-buntansha) |
MIZOBUCHI Satoshi Okayama University, University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (70311800)
ITANO Yoshitaro Okayama University, Graduate School of Medicine, Dentistry, & Pharmaceutical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (30127542)
ABE Koji Okayama University, Graduate School of Medicine, Dentistry, & Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20212540)
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Project Period (FY) |
2002 – 2004
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Keywords | Nerve growth factor / Antisense RNA oligonucleotide / Intractable pain |
Research Abstract |
1.We investigated the spatial and temporal patterns of c-Fos protein (Fos) expression in the dorsal horn of the spinal cord caused by plantar incision in the rat and the effects of pretreatment with local anesthetics. Our results indicate that 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. 2.We measured the mRNAs of cyclooxygenase(COX)-2, and trkB receptor in the spinal cord, and also brain-derived neurotrophic factor(BDNF) in the dorsal root ganglion(DRG) after an injection of formalin in the hind paw of a rat with L5 spinal nerve ligation(SNL)-induced neuropathy. We also measured c-fos mRNA expression in the spinal cord to clarify changes in neuronal activities in the central pathways. c-fos study indicates that the decrease in neuronal activities to inflammation pain in the spinal cord after SNL-induced neuropathy may play an important role in changing in the perception of acute pain. Increase in mRNA of BDNF after SNL-induced neuropathy suggests that overexpression of BDNF in the spinal cord could alleviate formalin-induced pain. 3.We established the real-time PCR method to quantify mRNA in the spinal level. Consequently, we became able to quantify a very small amount of neurotrophic factors. Furthermore, we got a technique of in situ hybridization and intrathecal administration of drugs. Antisense RNA of neurotrophic factors can be administered intrathecally in the neuropathic pain model.
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Research Products
(12 results)