Analgesic mechanism of Botulinum toxin in neuropathic pain

• Project/Area Number: 25893140
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Okayama University
• Principal Investigator: MARUHAMA Kotaro 岡山大学, 医歯(薬)学総合研究科, 助教 (60712792)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ボツリヌス毒素 / 神経伝達物質 / 三叉神経 / 神経障害性疼痛 / 軸索輸送 / 精製A型ボツリヌス毒素 / 知覚神経節

Outline of Final Research Achievements

BoNT/A heavy chain (Hc) was labeled with Thiol-Reactive Probes (Alexa-488) and injected into the dissociated rat trigeminal ganglion somata and the rat facial skin. Localization of BoNT/A-Hc was monitored in trigeminal ganglion neurons by confocal laser scanning microscopy.
BoNT/A-Hc was taken up by trigeminal ganglion neurons. This uptake was inhibited by colchicine treatment, which blocks axonal transport. Our data suggest that retrograde axonal transport of BoNT/A to sensory ganglion occurs following peripheral administration.

Research Products

• [Journal Article] Convergent nociceptive input to spinal dorsal horn neurons after peripheral nerve injury (2015)
  • Author(s): Terayama R, Kishimoto N, Yamamoto Y, Maruhama K, Tsuchiya H, Mizutani M, Iida S, Sugimoto T
  • Journal Title: Neurochem Res Volume: 40 Issue: 3 Pages: 438-445
  • DOI: 10.1007/s11064-014-1484-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Assessment of intraoral mucosal pain induced by the application of capsaicin (2014)
  • Author(s): Terayama R, Maruhama K, Tsuchiya H, Mizutani M, Iida S, Sugimoto T
  • Journal Title: Arch Oral Biol Volume: 59 Issue: 12 Pages: 1334-1341
  • DOI: 10.1016/j.archoralbio.2014.08.008
  • NAID: 120005477122
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ボツリヌス毒素を利用した神経障害性疼痛治療 (2015)
  • Author(s): 松香芳三、丸濵功太郎、山本由弥子、小熊惠二、松下治
  • Organizer: 第88回日本細菌学会総会
  • Place of Presentation: 長良川国際会議場
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] Relationship Between Neurotransmitter release within sensory ganglia and pain transmission (2015)
  • Author(s): K. Omoto, K. Maruhama, Y. Suzuki, K. Okura, Y. Matsuka
  • Organizer: IADR/AADR/CADR General Session & Exhibition
  • Place of Presentation: Boston
  • Year and Date: 2015-03-11 – 2015-03-14
• [Presentation] Neural excitation with positron emission tomography after tooth mechanical stimulation (2014)
  • Author(s): Katsuhiro Omoto, Kotaro Maruhama, Tomosada Sugimoto, Yoshizo Matsuka
  • Organizer: Society for Neuroscience 2014
  • Place of Presentation: Washington convention center
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] 末梢知覚神経節における神経伝達物質遊離抑制による情報伝達の変化 (2014)
  • Author(s): 大本勝弘、丸濵功太郎、田中紗友里、大倉一夫、杉本朋貞、松香芳三
  • Organizer: 第19回日本口腔顔面痛学会学術大会
  • Place of Presentation: 東京医科歯科大学特別講堂
  • Year and Date: 2014-11-01 – 2014-11-02
• [Presentation] 末梢投与された A 型ボツリヌス神経毒素の三叉神経における局在と軸索輸送 (2014)
  • Author(s): 山本由弥子、丸濵功太郎、松香芳三、美間健彦、後藤和義、横田憲治
  • Organizer: 第67回日本細菌学会中国・四国支部総会
  • Place of Presentation: 徳島文理大学薬学部
  • Year and Date: 2014-10-04 – 2014-10-05
• [Presentation] The axonal transport and analgesic effect of newly developed Botulinum neurotoxin type A (2014)
  • Author(s): Kotaro Maruhama, Yoshizo Matsuka, Yumiko Yamamoto, Ryuji Terayama, Tomosada Sugimoto
  • Organizer: Neuroscience 2014
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 末梢知覚神経節における神経伝達物質遊離抑制と鎮痛効果 (2014)
  • Author(s): 田中紗友里、大本勝弘、丸濵功太郎、松香芳三
  • Organizer: （社）日本補綴歯科学会 中国・四国支部学術大会
  • Place of Presentation: 倉敷芸文館
  • Year and Date: 2014-09-06 – 2014-09-07
• [Presentation] 知覚神経節における精製A型ボツリヌス毒素の疼痛抑制効果 (2014)
  • Author(s): 丸濵功太郎、松香芳三、寺山隆司、杉本朋貞
  • Organizer: 第119回日本解剖学会総会・全国学術集会
  • Place of Presentation: 栃木
• [Presentation] The axonal transport and analgesic effect of newly developed Botulinum neurotoxin type A (2014)
  • Author(s): Kotaro Maruhama, Yoshizo Matsuka, Yumiko Yamamoto, Ryuji Terayama, Tomosada Sugimoto
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] 一次求心ニューロンによる精製A型ボツリヌス毒素の 取り込みと軸索輸送 (2013)
  • Author(s): 丸濵功太郎、松香芳三、寺山隆司、窪木拓男、杉本朋貞
  • Organizer: 第55回歯科基礎医学会学術大会・総会
  • Place of Presentation: 岡山
• [Presentation] 一次求心ニューロンによる精製A型ボツリヌス毒素の取り込みと軸索輸送 (2013)
  • Author(s): 丸濵功太郎、寺山隆司、杉本朋貞
  • Organizer: 日本解剖学会第68回中国四国支部学術集会
  • Place of Presentation: 鳥取