Basic Research of Gene Therapy for Intractable Pain with siRNA

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591630
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Okayama University
• Principal Investigator: YOKOYAMA Masataka 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)
• Co-Investigator(Kenkyū-buntansha): ITANO Yoshitaro Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (30127542) ; MIZOBUCHI Satoshi University Hospital of Medicine & Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (70311800) ; MORITA Kiyoshi Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (40108171)
• Project Period (FY): 2005 – 2006
• Keywords: Intractable Pain / siRNA / Gene Therapy / BDNF

Research Abstract

To investigate which exon of BDNF is involved in inflammatory pain, we quantitated infIammation-induced expression of BDNF exons in the rat DRG. Rats received subcutaneous injections of complete Freund's adjuvant (CFA) into plantar surface of the left hind paw. InCFA-treated rats, the expressions of exon I in ipsilateral DRGincreased significantly. Our results support that inflammation increases total BDNF mRNA. Furthermore, our results indicate that exon I plays important role in increase in BDNF mRNA after inflammation.
Therefore, we targeted the exon I of BDNF for knock-down with siRNA. We created the two different siRNAs for exson I of BDNF. The intrathecal catheter was inserted 10 days before CFA injection. The two different siRNAs for the exon I of BDNF twice before CFA injection.
The pain behaviors were decreased by the administration of siRNAs, but not completed suppressed. The expression of BDNF was not completed suppressed in DRG after the administration of the two siRNAs.
In the future, We have to investigate how much doses of siRNA should be administered. We also have to check the timing when siRNA should be administerd.

Research Products

• [Journal Article] Altered response to formalin by L5 spinal nerve ligation in rats : a behavioral and molecular study. (2007)
  • Author(s): Kaku R, et al.
  • Journal Title: Anesth Analg 104 Pages: 936-943
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Epidural blood patch therapy for chronic whiplash-associated disorder. (2007)
  • Author(s): Ishikawa S, et al.
  • Journal Title: Anesth Analg (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Altered response to formal in by L5 spinal nerve ligation in rats : a behavioral and molecular study. (2007)
  • Author(s): Kaku R, Yokoyama M, Kobayashi H, Matsuoka Y, Sato T, Mizobuchi S, Itano Y, Morita K.
  • Journal Title: Anesth Analg 104 Pages: 936-43
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Epidural blood patch therapy for chronic whiplash-associated disorder. (2007)
  • Author(s): Ishikawa S, Yokoyama M, Mizobuchi S, Hashimoto H, Moriyama E. Morita K.
  • Journal Title: Anesth Analg (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic lateral sclerosis. (2005)
  • Author(s): Nagano I, et al.
  • Journal Title: J Neurol Sci 235 Pages: 61-68
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Beneficial effects of intrathecal IGF-1 administration in patients with amyotrophic lateral sclerosis. (2005)
  • Author(s): Nagano I, et al.
  • Journal Title: Neurol Res 27 Pages: 768-772
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The effects of continuous epidural anesthesia and analgesia on stress response and immune function in patients undergoing radical esophagectomy. (2005)
  • Author(s): Yokoyama M, et al.
  • Journal Title: Anesth Analg 101 Pages: 1521-1527
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] オピオイドの新しい知見 (2005)
  • Author(s): 石川慎一, 他
  • Journal Title: 緩和医療 13 Pages: 41-46
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic lateral sclerosis (2005)
  • Author(s): Nagano I, Ilieva H, Shiote M, Murakami T, Yokoyama M, ShojiM, Abe K.
  • Journal Title: J Neurol Sci 235 Pages: 61-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Beneficial effects of intrathecal IGF-1 administration in patients with amyotrophic lateral sclerosis. (2005)
  • Author(s): Nagano I, Shiote M, Murakami T, Kamada H, Hamakawa Y, Matsubara E, Yokoyama M, Morita K, Shoji M, Abe K.
  • Journal Title: Neurol Res 27 Pages: 768-72
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The effects of continuous epidural anesthesia and analgesia on stress response and immune function in patients undergoing radical esophagectomy. (2005)
  • Author(s): Yokoyama M, Itano Y, Katayama H, Morimatsu H, Takeda Y, Takahashi T, Nagano 0, Morita K.
  • Journal Title: Anesth Analg 101 Pages: 1521-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Update on opioid. (2005)
  • Author(s): Ishikawa S, Mizobuchi S, Nishie H, Matsusaki T, Fujii M, Abo K, Sato K, Nakatsuka H, Matsumi M, Yokoyama M, Morita K.
  • Journal Title: The Journal of Palliative Medicine 12 Pages: 41-6
  • Description: 「研究成果報告書概要(欧文)」より