Development of a new treatment for trigeminal neuron sensitization

• Project/Area Number: 22390365
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Prosthetic dentistry
• Research Institution: The University of Tokushima (2012-2013); Okayama University (2010-2011)
• Principal Investigator: MATSUKA Yoshizo 徳島大学, ヘルスバイオサイエンス研究部, 教授 (90243477)
• Co-Investigator(Kenkyū-buntansha): KUBOKI Takuo 岡山大学, 大学院・医歯薬学総合研究科, 教授 (00225195) ; YAMAMOTO Yumiko 岡山大学, 大学院・医歯薬学総合研究科, 助教 (20403496) ; KUMADA Ai 岡山大学, 岡山大学病院, 医員 (40610895)
• Co-Investigator(Renkei-kenkyūsha): OGUMA Keiji 岡山大学, 大学院・医歯薬学総合研究科, 教授 (00002262)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2013: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2010: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 三叉神経障害性疼痛モデル / 神経節細胞 / 疼痛行動 / 知覚神経節 / A型ボツリヌス毒素 / 遊離 / 神経内走行 / Ａ型ボツリヌス毒素 / 神経筋細胞 / 改良A型ボツリヌス毒素

Research Abstract

Fluorescein labeled botulinum toxin heavy chain which works for endocytosis was injected into rat face skin and found in ipsilateral trigeminal ganglion. The labeled botulinum toxin heavy chain was not found on the contralateral side or in the only fluorescein injection. The uptake was inhibited by colchicine treatment, which blocks axonal transport. Intradermal injection of botulinum toxin alleviates infraorbital nerve constriction induced thermal hyperalgesia in an operant assay. Direct application of botulinum toxin to dorsal root ganglia reversed the sciatic nerve entrapment induced decreases in withdrawal thresholds.

Research Products

• [Journal Article] 非歯原性歯痛の発症機序,診断,治療 (2013)
  • Author(s): 松香芳三
  • Journal Title: 四国歯学会雑誌 Volume: 25 Pages: 29-38
  • NAID: 120005832453
• [Journal Article] Primary treatment of temporomandibular disorders: The Japanese Society for the temporomandibular joint evidence-based clinical practice guidelines, 2nd edition (2013)
  • Author(s): Yuasa H, Kino K, Kubota E, Kakudo K, Sugisaki M, Nishiyama A, Matsuka Y, Ogi N
  • Journal Title: Japanese Dental Science Review Volume: 49 Issue: 3 Pages: 89-98
  • DOI: 10.1016/j.jdsr.2013.05.002
  • NAID: 50009115431
  • Peer Reviewed
• [Journal Article] Occlusal discomfort syndrome (2013)
  • Author(s): 玉置勝司，石垣尚一，小川 匠，尾口仁志，加藤隆史，菅沼岳史， 島田 淳，貞森紳丞，築山能大， 西川洋二，鱒見進一，山口泰彦， 會田英紀，小野高裕，近藤尚知， 塚崎弘明，笛木賢治，藤澤政紀， 松香芳三，馬場一美，古谷野 潔
  • Journal Title: Annals of Japan Prosthodontic Society Volume: 5 Issue: 4 Pages: 369-386
  • DOI: 10.2186/ajps.5.369
  • NAID: 10031202885
  • ISSN: 1883-4426, 1883-6860
  • Peer Reviewed
• [Journal Article] Self-reported aural symptoms, headache and temporomandibular disorders in Japanese young adults (2013)
  • Author(s): Akhter R et al
  • Journal Title: BMC Musculoskelet Disord Volume: 14 Issue: 1 Pages: 58-64
  • DOI: 10.1186/1471-2474-14-58
  • Peer Reviewed
• [Journal Article] Application of purified botulinum type A neurotoxin to treat experimental trigeminal neuropathy in rats and patients with urinary incontinence and prostatic hyperplasia (2012)
  • Author(s): Matsuka Y, Yokoyama T, Yamamoto Y, Suzuki T, Nishikawa A, Ohyama T, Watanabe T, Kuboki T, Nagai A, Oguma K.
  • Journal Title: Journal of Toxicology Volume: (online journal) Pages: 648384-648384
  • DOI: 10.1155/2012/648384
  • Peer Reviewed
• [Journal Article] Intradermal injection of Botulinum toxin type A alleviates infraorbital nerve constriction-induced thermal hyperalgesia in an operant assay (2012)
  • Author(s): Kumada A, Matsuka Y, Spigelman I, Maruhama K, Yamamoto Y, Neubert JK, Noland TA, Watanabe K, Maekawa K, Kamioka H, Yamashiro T, Kuboki T, Oguma K.
  • Journal Title: Journal of Oral Rehabilitation Volume: 39 Issue: 1 Pages: 63-72
  • DOI: 10.1111/j.1365-2842.2011.02236.x
  • Peer Reviewed
• [Journal Article] Occlusal Dysesthesia: a qualitative systematic review of the epidemiology, aetiology and management (2012)
  • Author(s): Hara ES et al
  • Journal Title: Journal of Oral Rehabilitation Volume: 39 Issue: 8 Pages: 630-638
  • DOI: 10.1111/j.1365-2842.2012.02300.x
  • Peer Reviewed
• [Journal Article] Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions-a taskforce report (2011)
  • Author(s): Svensson P, Baad-Hansen L, Pigg M, List T, et.al.
  • Journal Title: Journal of Oral Rehabilitation Volume: 38(5) Issue: 5 Pages: 366-394
  • DOI: 10.1111/j.1365-2842.2010.02196.x
  • Peer Reviewed
• [Journal Article] Peripheral administration of botulinum toxin type A neurotoxin reverses trigeminal neuropathic pain symptoms (2011)
  • Author(s): Kumada A, Matsuka Y, Spigelman I, Neubert JK, Nolan TA, Yamamoto Y, Sato K, Watanabe K, Kuboki T, Oguma K.
  • URL: http://posters.f1000.com/PosterList?posterID=763
  • Peer Reviewed
• [Journal Article] Peripheral administration of botulinum toxin type A neurotoxin reverses trigeminal neuropathic pain symptoms (2011)
  • Author(s): Kumada A, Matsuka Y, Spigelman I, Neubert JK, Nolan TA, Yamamoto Y, Sato K, Watanabe K, Kuboki T, Oguma K
  • Journal Title: http://posters.f1000.com/PosterList?posterID=763
• [Journal Article] Peripheral administration of Botulinum toxin type A decreases exaggerated neurotransmitter release and reverses neuropathy-induced gene expression changes in trigeminal ganglia (2010)
  • Author(s): Kumada A, Matsuka Y, Kitamura Y, Spigelman I, Ishihara Y, Yamamoto Y, Hikasa T, Sonoyama W, Kamioka H, Yamashiro T, Kuboki T, Oguma K.
  • URL: http://posters.f1000.com/Conferences?confID=3&sectID=null&posterID=266.12
  • Peer Reviewed
• [Journal Article] Peripheral administration of Botulinum toxin type A decreases exaggerated neurotransmitter release and reverses neuropathy-induced gene expression changes in trigeminal ganglia (2010)
  • Author(s): Kumada A, Matsuka Y, Kitamura Y, Spigelman I, Ishihara Y, Yamamoto Y, Hikasa T, Sonoyama W, Kamioka H, Yamashiro T, Kuboki T, Oguma K
  • Journal Title: http://posters.f1000.com/Conferences?confID=3&sect ID=null&posterID=266.12
• [Presentation] 神経障害性疼痛における末梢知覚神経節での神経伝達物質の関与 (2014)
  • Author(s): 黒厚子璃佳, 岩田こころ, 大本勝弘, 丸濵功太郎, 松香芳三
  • Organizer: 四国歯学会
  • Place of Presentation: (徳島県)徳島大学
  • Year and Date: 2014-03-20
• [Presentation] 神経障害性疼痛における末梢知覚神経節での神経伝達物質の関与 (2014)
  • Author(s): 黒厚子璃佳, 岩田こころ, 大本勝弘，丸濵功太郎, 松香芳三
  • Organizer: 四国歯学会
  • Place of Presentation: 徳島大学（徳島県）
• [Presentation] 口腔顔面痛の疼痛伝達メカニズムと新規治療法の開発-知覚神経節細胞からの神経伝達物質遊離- (2013)
  • Author(s): 松香芳三
  • Organizer: 日本歯科基礎医学会
  • Place of Presentation: (岡山県)岡山コンベンションセンター
  • Year and Date: 2013-09-22
• [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: 日本歯科基礎医学会
  • Place of Presentation: (岡山県)岡山コンベンションセンター
  • Year and Date: 2013-09-21
• [Presentation] Botulinum toxin endocytosis into trigeminal neurons alleviates neuropathic pain (2013)
  • Author(s): Maruhama K, Matsuka Y, Yamamoto Y, Terayama R, Komi K, Ono M, Maekawa K, Kamioka H, Yamashiro T, Sugimoto T, Matsushita O, Kuboki T.
  • Organizer: International Association for Dental Research
  • Place of Presentation: (アメリカ)ワシントン州コンベンションセンター
  • Year and Date: 2013-03-22
• [Presentation] 神経毒素成分を精製したA型ボツリヌス毒素の三叉神経への効果 (2013)
  • Author(s): 丸濵功太郎, 松香芳三, 古味佳子, 大野光昭, 前川賢治, 窪木拓男
  • Organizer: 日本補綴歯科学会
  • Place of Presentation: (福岡県)福岡国際会議場
• [Presentation] 神経毒素成分を精製したA型ボツリヌス毒素の三叉神経への効果 (2013)
  • Author(s): 丸濵功太郎, 松香芳三, 古味佳子, 大野光昭, 前川賢治, 窪木拓男
  • Organizer: 日本補綴歯科学会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] Botulinum toxin endocytosed trigeminal neurons alleviates neuropathic pain (2013)
  • Author(s): Omoto K, Suzuki Y, Maruhama K, Yamamoto Y, Terayama R, Spigelman I, Kamioka H, Maekawa K, Sugimoto T, Matsushita O, Kuboki T, Matsuka Y
  • Organizer: Asia Academic Congress for Temporomandibular Joint
  • Place of Presentation: International Communication Branch (China)
• [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: 日本歯科基礎医学会
  • Place of Presentation: 岡山コンベンションセンター（岡山県）
• [Presentation] 口腔顔面痛の疼痛伝達メカニズムと新規治療法の開発－知覚神経節細胞からの神経伝達物質遊離－ (2013)
  • Author(s): 松香芳三
  • Organizer: 日本歯科基礎医学会
  • Place of Presentation: 岡山コンベンションセンター（岡山県）
  • Invited
• [Presentation] 口腔顔面痛の疼痛伝達メカニズムと新規治療法の開発 知覚神経節細胞からの神経伝達物質の遊離 (2013)
  • Author(s): 松香芳三
  • Organizer: 四国歯学会
  • Place of Presentation: 徳島大学（徳島）
  • Invited
• [Presentation] Botulinum toxin endocytosis into trigeminal neurons alleviates neuropathic pain (2013)
  • Author(s): Maruhama K et al
  • Organizer: International Association for Dental Research
  • Place of Presentation: Washington State Convention Center (USA)
• [Presentation] 神経障害性疼痛へのポツリヌス毒素の効果 (2012)
  • Author(s): 松香芳三, 丸濵功太郎, 三宅 愛, 山本由弥子, 前川賢治, 古味桂子, 園山 亘, 小熊惠二, 窪木拓男
  • Organizer: 日本歯科医学会総会
  • Place of Presentation: (大阪府)インテックス大阪
  • Year and Date: 2012-11-11
• [Presentation] 神経毒素成分を精製したA型ボツリヌス毒素の三叉神経への取り込みと輸送 (2012)
  • Author(s): 丸濵功太郎, 松香芳三, 山本由弥子, 寺山隆司, 古味佳子, 大野充昭, 前川賢治, 上岡 寛, 山城 隆, 杉本朋貞, 松下治, 小熊恵二, 窪木拓男
  • Organizer: 日本口腔顔面痛学会
  • Place of Presentation: (東京都)慶應義塾大学
  • Year and Date: 2012-11-03
• [Presentation] 神経障害性疼痛へのポツリヌス毒素の効果 (2012)
  • Author(s): 松香芳三 他
  • Organizer: 日本歯科医学会総会
  • Place of Presentation: インテック大阪（大阪）
• [Presentation] 神経毒素成分を精製したA型ボツリヌス毒素の三叉神経への取り込みと輸送 (2012)
  • Author(s): 丸濵功太郎 他
  • Organizer: 日本口腔顔面痛学会
  • Place of Presentation: 慶應大学（東京）
• [Presentation] Botulinum neurotoxin type A endocytosis into trigeminal neurons and its effect on neuropathic pain behavior (2011)
  • Author(s): Maruhama K, Kumada A, Matsuka Y, Spigelman I, Neubert JK, Nolan TA, Yamamoto Y, Suzuki T, Maekawa K, Kamioka H, Yamashiro T, Kuboki T, Oguma K.
  • Organizer: Society for Neuroscience
  • Place of Presentation: (アメリカ)ワシントン州コンベンションセンター
  • Year and Date: 2011-11-15
• [Presentation] Botulinum neurotoxin type A endocytosis into trigeminal neurons and its effect on neuropathic pain behavior (2011)
  • Author(s): Maruhama K
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC
  • Year and Date: 2011-11-15
• [Presentation] Medical application of clostridal toxins; 1) Clostridium botulinum neurotoxin (2011)
  • Author(s): Oguma K, Yamamoto Y, Suzuki T, Yokoyama T, Matsuka Y, Arimitsu H, Kuboki T.
  • Organizer: International Union of Microbiological Societies 2011 Congress, Sapporo
  • Place of Presentation: (北海道)札幌コンベンションセンター
  • Year and Date: 2011-09-09
• [Presentation] Medical application of clostridal toxins ; 1) Clostridium botulinum neurotoxin (2011)
  • Author(s): Oguma K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Hokkaido
  • Year and Date: 2011-09-09
• [Presentation] Botulinum toxin type A neurotoxin endocytosis into trigeminal neuron and its effect onto neuropathic pain beahavior (2011)
  • Author(s): Kumada A, Matsuka Y, Yamamoto Y, Suzuki T, Spigelman I, Neubert JK, Nolan TA, Watanabe K, Maruhama K, Maekawa K, Kamioka H, Yamashiro T, Kuboki T, Oguma K.
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: (北海道)札幌コンベンションセンター
  • Year and Date: 2011-09-07
• [Presentation] Botulinum toxin type A neurotoxin endocytosis into trigeminal neuron and its effect onto neuropathic pain beahavior (2011)
  • Author(s): Kumada A
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Hokkaido
  • Year and Date: 2011-09-07
• [Presentation] 知覚神経節へのボツリヌス毒素投与による神経障害性疼痛モデルラットの疼痛行動変化 (2011)
  • Author(s): 渡邊一博, 松香芳三, 丸濵功太郎, 熊田 愛, 前川賢治, 園山 亘, 窪木拓男
  • Organizer: 日本補綴歯科学会中国・四国支部学術大会
  • Place of Presentation: (岡山県)岡山大学
  • Year and Date: 2011-09-04
• [Presentation] 知覚神経節へのボツリヌス毒素投与による神経障害性疼痛モデルラットの疼痛行動変化 (2011)
  • Author(s): 渡邊一博
  • Organizer: 日本補綴歯科学会中国・四国支部学術大会
  • Place of Presentation: 岡山
  • Year and Date: 2011-09-04
• [Presentation] 三叉神経領域における神経障害性疼痛に対する改良A型ボツリヌス毒素の効果 (2011)
  • Author(s): 熊田愛
  • Organizer: 日本補綴歯科学会
  • Place of Presentation: 広島
  • Year and Date: 2011-05-20
• [Presentation] 三叉神経領域における神経障害性疼痛に対する改良A型ボツリヌス毒素の効果 (2011)
  • Author(s): 熊田 愛, 松香芳三, 丸濱功太郎, 前川賢治, 窪木拓男
  • Organizer: 日本補綴歯科学会
  • Place of Presentation: (広島県)廣島国際会議場
• [Presentation] Peripheral administration of Botulinum toxin type A neurotoxin reverses trigeminal neuropathic pain symptoms (2010)
  • Author(s): Kumada A, Matsuka Y, Spigelman I, Neubert JK, Nolan TA, Yamamoto Y, Satoh K, Watanabe K, Kuboki T, Oguma K.
  • Organizer: Society for Neuroscience
  • Place of Presentation: (アメリカ)サンディエゴコンベンションセンター
  • Year and Date: 2010-11-15
• [Presentation] Peripheral administration of Botulinum toxin type A neurotoxin reverses trigeminal neuropathic pain symptoms (2010)
  • Author(s): Kumada A, Matsuka Y, Spigelman I, Neubert JK, Nolan TA, Yamamoto Y, Satoh K, Watanabe K, Kuboki T, Oguma K
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2010-11-15
• [Presentation] Pepripehral administration of Botlinum toxin type A neurotoxin reverses trigeminal thermal hyperalgesia (2010)
  • Author(s): Kumada A, Matsuka Y, Spigelman I, Neubert JK, Nolan TA, Yamamoto Y, Sato K, Watanabe K, Yamamoto K, Murakami K, Kuboki T, Oguma K.
  • Organizer: Asian Academy of Craniomandibular Disorders
  • Place of Presentation: (福岡県)九州大学
  • Year and Date: 2010-10-03
• [Presentation] 特定歯の疼痛が繰り返し増強される神経障害性疼痛患者の一例 (2010)
  • Author(s): 瀧内博也, 三木春奈, 北村洋一, 前川賢治, 松香芳三, 窪木拓男
  • Organizer: 日本口腔顔面痛学会
  • Place of Presentation: 博多
  • Year and Date: 2010-10-03
• [Presentation] Pepripehral administration of Botlinum toxin type A neurotoxin reverses trigeminal thermal hyperalgesia (2010)
  • Author(s): Kumada A, Matsuka Y, Spigelman I, Neubert JK, Nolan TA, Yamamoto Y, Sato K, Watanabe K, Yamamoto K, Murakami K, Kuboki T, Oguma K
  • Organizer: Asian Academy of Craniomandibular Disorders
  • Place of Presentation: Hakata
  • Year and Date: 2010-10-03
• [Presentation] 電子痛覚測定装置による歯根膜感覚の客観的評価の検討 (2010)
  • Author(s): 平井真也, 小川匠, 松香芳三, 重田優子, 安藤栄里子, 平林里大, 井川知子, 笠間慎太郎, 福島俊士, 窪木拓男, G.T.Clark
  • Organizer: 日本顎関節学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-25
• [Presentation] Association of TMJ-pain, headache and bruxism in non-patient young adults (2010)
  • Author(s): Hara ES, Miyawaki S, Minakuchi H, Kataoka T, Matsuka Y, Yamashiro T, Takano-Yamamoto T, Kuboki T
  • Organizer: International Association for Dental Research
  • Place of Presentation: Barcelona
  • Year and Date: 2010-07-16
• [Book] 歯原性歯痛の診断手順,異所性疼痛メカニズム (2013)
  • Author(s): 松香芳三
  • Publisher: 医歯薬出版, 歯界展望