Mechanism of Shakuyaku-kannzo-to reduces paclitaxel-induced neuropathic pain

• Project/Area Number: 24590325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Fukushima Medical University
• Principal Investigator: Kimura Junko 福島県立医科大学, 医学部, 教授 (10186322)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 抗がん薬 / 芍薬甘草湯 / 神経痛 / T型Ca電流 / ホールセルクランプ法 / HEK２９３細胞 / パクリタキセル / 副作用 / Ｔ型カルシウムチャネル / Cav3.2 / HEK293細胞 / ホールセルクランプ / 濃度反応曲線 / Shakuyakukanzoto / IKur / Kv2.1 / Shakuyaku / Kanzo / H9c2 cells / glycirrhizin / whole cell clamp / 英国オックスフォード大学

Outline of Final Research Achievements

Paclitaxel is widely used for the treatment of solid malignant tumor, but its adverse effect is peripheral neuralgia. Shakuyaku-kanzo-to (SKT) is known to reduce pain of peripheral neuralgia induced by paclitaxel in mice. It was also reported that the voltage-dependent T-type Ca channels (Cav3.2 ) is involved in neuropathic pain. Therefore we investigated whether SKT inhibits T type Ca current using HEK cells expressing human T type Ca current (hCav3.2). We found that SKT inhibited T-type Ca current in HEK293 cells using the whole cell patch clamp method. SKT at 10 mg/ml completely inhibited the T type Ca current. The IC50 value of SKT was 1.3 mg/ml、and Hill coefficient was 1.1. Our result suggests that the inhibition of T-type Ca current may be involved in the analgesic effect of Shakuyaku-kanzo-to on paclitaxel-induced neuralgia.

Research Products

• [Journal Article] The inhibitory effect of paclitaxel on (Kv2.1) K current in H9c2 cells. (2015)
  • Author(s): Kitamura N, Sakamoto K, Ono T, Kimura J
  • Journal Title: Fukushima Journal of Medical Science Volume: 61 Pages: 47-53
  • NAID: 130005087004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The inhibitory effect of paclitaxel on (Kv2.1)K+ cyrrebt ub H9c2 cells. (2015)
  • Author(s): Naoko Kitamura, Kazuho Sakamoto, Tomoyuki Ono, Junko Kimura
  • Journal Title: Fukushima Journal of Medical Science Volume: 61 Pages: 1-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] THE INHIBITORY EFFECT OF SHAKUYAKUKANZOTO ON K⁺ CURRENT IN H9c2 CELLS (2014)
  • Author(s): Azusa Suganami , Kazuho Sakamoto, Tomoyuki Ono, Hiroake Watanabe, Nahoko Hijioka, Masahiro Murakawa, Junko Kimura
  • Journal Title: FUKUSHIMA JOURNAL OF MEDICAL SCIENCE Volume: 60 Issue: 1 Pages: 22-30
  • DOI: 10.5387/fms.2013-16
  • NAID: 130003396126
  • ISSN: 0016-2590, 2185-4610
  • Peer Reviewed / Open Access / Acknowledgement Compliant