Intra-thecal Noggin Injection For Chronic Constriction Injury partially Ameliorates Neuropathic Pain State In the Rat.

• Project/Area Number: 24592186
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Chiba University
• Principal Investigator: MURATA ATSUSHI 千葉大学, 医学部附属病院, 准教授 (20344997)
• Co-Investigator(Kenkyū-buntansha): YAMAZAKI Masashi 筑波大学, 医学医療系, 教授 (50281712) ; 大河 昭彦 千葉大学, 医学(系)研究科(研究院), 講師 (30312945)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: neuropathic pain / CCI / mRNA / microarray / Noggin / Alzet pump / rats / astrocytes / 神経障害性疼痛 / 坐骨神経結紮モデル / アロジニア / BMP4 / くも膜下腔 / Western blot

Outline of Final Research Achievements

We find that Noggin mRNA is down-regulated in the lumber enlargement two weeks after Chronic Constriction injury (CCI) in the rats by a Microarray and RT-PCR study. In the present study, we injected Noggin protein intrathecally using Alzet-mini pump for CCI model and see the neuropathic pain state using von Frey test for five weeks. Two weeks after CCI, Alzet-mini pump (14 days) with Noggin was inserted intrathecally. Rats whose Noggin concentration was 2microg/ml showed significantly less hyper-sensation compared with control.
We next compared intrathecal Noggin injection (2microg/ml) with BMP4 (2microg/ml), or BMP4 (4microg/ml) +Noggin (4microg/ml) injection, and compared statistically with control. Noggin injection only showed statistically significant less hyper-sensation than others. Fluorescent immunohistochemistry showed Noggin injection partially decreased astrocytes accumulation in the dorsal horn compared with PBS control one week after intrathecal Noggin injection.

Research Products

• [Journal Article] Coexistence of amyotrophic lateral sclerosis with neuro-Behçet's disease presenting as a longitudinally extensive spinal cord lesion: clinicopathologic features of an autopsied patient. (2014)
  • Author(s): Sato T, Ouchi H, Shimbo J, Sato A, Yamazaki M, Hashidate H, Igarashi S, Kakita A.
  • Journal Title: Neuropathology Volume: 34 Pages: 185-189
  • Peer Reviewed
• [Journal Article] Delayed granulocyte colony-stimulating factor treatment in rats attenuates mechanical allodynia induced by chronic constriction injury of the sciatic nerve. (2014)
  • Author(s): Koda M, Furuya T, Kato K, Mannoji C, Hashimoto M, Inada T, Kamiya K, Ota M, Maki S, Okawa A, Takahashi K, Ishikawa T, Yamazaki M.
  • Journal Title: Spine Volume: 39 Pages: 192-197
  • Peer Reviewed
• [Journal Article] Neuroprotective therapy with granulocyte colony-stimulating factor in acute spinal cord injury: a comparison with high-dose methylprednisolone as a historical control. (2014)
  • Author(s): Kamiya K, Koda M, Furuya T, Kato K, Takahashi H, Sakuma T, Inada T, Ota M, Maki S, Okawa A, Ito Y, Takahashi K, Yamazaki M.
  • Journal Title: Eur Spine J Volume: Epub
  • Peer Reviewed
• [Journal Article] Transplantation of human bone marrow stromal cell-derived neuroregenrative cells promotes functional recovery after spinal cord injury in mice. (2014)
  • Author(s): Mannoji C, Koda M, Kamiya K, Dezawa M, Hashimoto M, Furuya T, Okawa A, Takahashi K, Yamazaki M.
  • Journal Title: Acta Neurobiol Exp (Wars) Volume: 74 Pages: 479-488
  • Peer Reviewed
• [Journal Article] Intramedullary hemorrhage caused by spinal cord hemangioblastoma: a case report. (2014)
  • Author(s): Koda M, Mannoji C, Itabashi T, Kita T, Murakami M, Yamazaki M, Aramomi M, Ikeda O, Furuya T.
  • Journal Title: BMC Res Notes Volume: 7 Issue: 1 Pages: 823-823
  • DOI: 10.1186/1756-0500-7-823
  • Peer Reviewed
• [Journal Article] Treatment with basic fibroblast growth factor-incorporated gelatin hydrogel does not exacerbate mechanical allodynia after spinal cord contusion injury in rats. (2013)
  • Author(s): Furuya T, Hashimoto M, Koda M, Murata A, Okawa A, Dezawa M, Matsuse D, Tabata Y, Takahashi K, Yamazaki M.
  • Journal Title: J Spinal Cord Med. Volume: 36 Pages: 134-139
  • Peer Reviewed
• [Journal Article] Granulocyte colony-stimulating factor reduced neuropathic pain associated with thoracic compression myelopathy: report of two cases. (2013)
  • Author(s): Yamazaki M, Sakuma T, Kato K, Furuya T, Koda M.
  • Journal Title: J Spinal Cord Medicine Volume: 36 Pages: 40-43
  • Peer Reviewed
• [Journal Article] Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of thoracic myelopathy: a multicenter prospective controlled trial. (2012)
  • Author(s): Sakuma T, Yamazaki M, Okawa A.
  • Journal Title: Spine Volume: 37 Pages: 1475-8
  • NAID: 10031169801
  • Peer Reviewed
• [Journal Article] Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial. (2012)
  • Author(s): Takahashi H, Yamazaki M.
  • Journal Title: Eur Spine J Volume: 21 Pages: 2580-2587
  • Peer Reviewed
• [Presentation] Intrathecal Noggin Injection For Chronic Constriction Injury partially Ameliorates Neuropathic Pain State In the Rat. (2013)
  • Author(s): Masayuki Hashimoto1, Masao Koda2, Atsushi Murata2, Kazuhisa Takahashi2
  • Organizer: Cervical Spine Research Society
  • Place of Presentation: Los Angels, USA
• [Presentation] ラット坐骨神経結紮モデルに対するNogginくも膜下腔投与の有効性について (2013)
  • Author(s): 橋本将行 国府田正雄 古矢丈雄 村田淳 高橋和久
  • Organizer: 日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉市
• [Presentation] ラット神経障害性疼痛モデルにおけるNogginタンパクのくも膜下腔投与による疼痛の軽減 (2012)
  • Author(s): 橋本将行、大河昭彦、山崎正志
  • Organizer: 第1259回千葉医学会整形外科例会
  • Place of Presentation: 千葉大学医学部附属病院