Study of Mechanism and Gene Therapy for Cancer Pain in Bone Tumor Model

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591631
• 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: 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)
• Co-Investigator(Kenkyū-buntansha): 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) ; 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 / ASIC / Gene Therapy / BDNF

Research Abstract

We tried to establish the animal model of bone tumor, but we could not culture the cancer cell. Therefore, we changed the animal model to chronic pain. We investigated the expression of acid-sensing ion channel 3 (ASIC3) in L5 spinal nerve ligation (SPNL) model. ASIC3 is believed to express in inflammation and cancer pain.
The L5 SPNL increased the proportion of ASIC3-immunoreactive (ir) neurons in the ipsilateral L4 dorsal root ganglion (DRG) compared to sham-operated rats.
The cell size analysis demonstrated that the proportion of large(> 1200 mm2) ASIC3-ir neurons in the ipsilateral L4 DRG significantly increased after L5 SPNL. In the ipsilateral L5 DRG, the proportion of ASIC3-ir neurons was barely affected by the treatment. However, L5 SPNL increased the proportion of small (< 1200 mm2) ASIC3-neurons and decreased that of large ir neurons compared to sham-operated animals.
The double immunofluorescence method revealed the increase of sensory neurons which co-expressed ASIC3 and BDNF in L4 DRG ipsilateral to L5 SPNL. In ipsilateral L5 DRG, however, such neurons severely decreased after L5 SPNL.
These findings may suggest that ASIC3 is associated with hyperalgesia by mechanical stimulus and inflammation in L5 SPNL models.

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