Development of a novel analgesic method for cancer pain through the brain-derived neurotrophic factor

• Project/Area Number: 26670694
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Kawasaki Medical School
• Principal Investigator: NAKATSUKA HIDEKI 川崎医科大学, 医学部, 教授 (70263580)
• Co-Investigator(Kenkyū-buntansha): MAESHIMA Kyoichiro 川崎医科大学, 医学部, 講師 (20549852)
• Research Collaborator: ITANO Yoshitaro ; TSUGE Msatsugu
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 骨転移癌性疼痛モデル / 脊髄神経 / BDNF / TrkB isoform2 / 発現ベクター / 後根神経節 / ＢＤＮＦ / ＴｒｋＢ / 遺伝子治療 / ＴｒＫＢ

Outline of Final Research Achievements

The brain-derived neurotrophic factor (BDNF) is necessary for nerve growth. BDNF in the dorsal root ganglion (DRG) and also modulates the pain transduction from the peripheral nociceptor.
One of TrkB receptors (isoform1), which has tyrosine kinase (tk) domain, acts as a pain modulator. If the other isoform (isoform2) , which dose not have tk domain, competitively block the binding of BDNF to isoform1, we could expect some effect against pain. Expression vector, constructed by TrkB-isoform2 gene-GFP gene-Tag (FLAG, S-Tag) after pCMV promoter, produced TrkB receptors with the transmembrane domain (TM+) and without the (TM-). Both TM+ group and TM- group in the expression vector administration group showed an analgesic effect. Pain-related behavior assessed by the von Frey tests showed hyperalgesia from day 7 after cancer cell administration. The expression of BDNF mRNA in the affected side of DRG at L3 increased compared with the unaffected side.

Research Products

• [Presentation] New Analgesia of Cancer Pain Through the Brain-derived Neurotrophic Factor. (2015)
  • Author(s): Masatsugu Tsuge., Yoshihisa Fujita., Hideki Nakatsuka.
  • Organizer: 2015 American Society of Anesthesiologists Annual Meeting
  • Place of Presentation: San Diego Convention Center(San Diego)
  • Year and Date: 2015-10-27
• [Presentation] 癌性疼痛の新しい鎮痛 (2015)
  • Author(s): 柘植雅嗣、大内田守、中塚秀輝
  • Organizer: 第７３回日本疼痛学会
  • Place of Presentation: 市民会館崇城大学ホール（熊本）
  • Year and Date: 2015-07-04