Involvement of TRPA1 in oral cancer-induced mechanical pain

• Project/Area Number: 26893243
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: Ono Kentaro 九州歯科大学, 歯学部, 准教授 (40316154)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: TRPA1 / P2X3 / ATP / ガン性疼痛 / 接触痛 / P2X2 / Cancer pain / Mechanical allodynia

Outline of Final Research Achievements

Oral cancer induces pain during meals when food and teeth touch on cancer region. In previous studies, it has been reported that adenosine triphosphate released from cancer causes mechanical pain. However, it is unclear which mechano-sensitive channels are involved. In this study, we investigated whether the mechano-sensitive channel TRPA1 is related in cancer-induced mechanical pain. Consequently, we revealed that mechanical pain is mediated by sensitization of TRPA1 following activation of P2X3 in the response to adenosine triphosphate.

Research Products

• [Int'l Joint Research] New York University(米国)
• [Journal Article] Distinct TRPV1- and TRPA1-based mechanisms underlying enhancement of oral ulcerative mucositis-induced pain by 5-fluorouracil. (2016)
  • Author(s): Yamaguchi, K., Ono, K., Hitomi, S., Ito, M., Nodai, T., Goto, T., Harano, N., Watanabe, S., Inoue, H., Miyano, K., Uezono, Y., Matoba, M., Inenaga, K.
  • Journal Title: Pain Volume: 157 Issue: 5 Pages: 1004-1020
  • DOI: 10.1097/j.pain.0000000000000498
  • Peer Reviewed / Open Access
• [Journal Article] 癌性疼痛、そして口内炎疼痛 (2015)
  • Author(s): 小野堅太郎、人見涼露、稲永清敏
  • Journal Title: 日本歯科評論 Volume: 75 Pages: 129-135
• [Journal Article] Novel methods of applying direct chemical and mechanical stimulation to the oral mucosa for traditional behavioral pain assays in conscious rats. (2015)
  • Author(s): Hitomi S, Ono K, Miyano K, Ota Y, Uezono Y, Matoba M, Kuramitsu S, Yamaguchi K, Matsuo K, Seta Y, Harano N, Inenaga K.
  • Journal Title: J Neurosci Methods Volume: 239 Pages: 162-169
  • DOI: 10.1016/j.jneumeth.2014.10.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Demethylating drugs as novel analgesics for cancer pain. Clin Cancer Res. (2014)
  • Author(s): Viet CT, Dang D, Ye Y, Ono K, Campbell RR, Schmidt BL.
  • Journal Title: Clin Cancer Res Volume: 20 Issue: 18 Pages: 4882-93
  • DOI: 10.1158/1078-0432.ccr-14-0901
  • Peer Reviewed
• [Journal Article] Adenosine triphosphate drives head and neck cancer pain through P2X2/3 heterotrimers. (2014)
  • Author(s): Ye Y, Ono K, Bernabe DG, Viet CT, Pickering V, Dolan JC, Hardt M, Ford AP, Schmidt BL.
  • Journal Title: Acta Neuropathol Commun Volume: 2 Issue: 1 Pages: 62-62
  • DOI: 10.1186/2051-5960-2-62
  • Peer Reviewed
• [Presentation] 抗癌薬5-フルオロウラシル投与後の口内炎誘発疼痛にTRPV1とTRPA1が関与する (2015)
  • Author(s): 山口喜一郎, 小野堅太郎, 人見涼露, 野代知孝, 伊藤美紗, 左合徹平, 原野望, 稲永清敏
  • Organizer: 三叉神経領域の感覚－運動統合機能研究会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-29
• [Presentation] Analgesic effect of hangeshashinto on oral ulcer-induced pain in rats. (2015)
  • Author(s): Hitomi, S., Ono, K., Yamaguchi, K., Omiya, Y., Terawaki, K. and Inenaga, K.
  • Organizer: The 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Primary nociceptive modulation via pigmentation-dependent dopaminergic signaling in skin. (2015)
  • Author(s): K. Ono, Y. Ye, CT. Viet, D. Dang, S. Hitomi, K. Inenaga and BL. Schmidt
  • Organizer: The 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] The ethanol metabolite acetaldehyde induces the sensation of thirst. (2015)
  • Author(s): I. Ujihara, K. Inenaga, S. Hitomi, K. Ono and Y. Kakinoki.
  • Organizer: The 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Effects of anti-cancer drugs on pain induction in a rat stomatitis model. (2015)
  • Author(s): K. Yamaguchi, S. Hitomi, K. Ono, N. Harano, S. Watanabe, K. Inenaga
  • Organizer: The 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Analgesic effect of Hangeshashinto, a traditional Japanese medicine, on oral ulcer-induced pain in rats. (2015)
  • Author(s): S. Hitomi, K. Ono, K. Yamaguchi, Y. Omiya, K. Terawaki and K. Inenaga.
  • Organizer: Asia-Pacific Conference
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2015-01-24
• [Presentation] Tyrosinase-dependent skin dopamine mediates heat pain sensitivity. (2015)
  • Author(s): K. Ono, Y. Ye, CT. Viet, D. Dang, S. Hitomi, K. Inenaga and BL. Schmidt.
  • Organizer: Asia-Pacific Conference
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2015-01-24
• [Presentation] Effects of anti-cancer drugs on oral ulcer-induced pain in rat model. (2015)
  • Author(s): K. Yamaguchi, S. Hitomi, K. Ono, N. Harano, S. Watanabe, K. Inenaga.
  • Organizer: Asia-Pacific Conference
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2015-01-24
• [Presentation] The action of the ethanol metabolite acetaldehyde on water and salt intake in rats. (2015)
  • Author(s): I. Ujihara, S. Hitomi, K. Ono, Y. Kakinoki, K. Inenaga.
  • Organizer: Asia-Pacific Conference
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2015-01-24
• [Presentation] Analgesic effect of Hangeshashinto, a traditional Japanese medicine, on oral ulcer-induced intraoral pain in rats. (2014)
  • Author(s): S. Hitomi, K. Ono, Y. Oomiya, K. Terawaki, A. Kaneko, Y. Uezono, K. Inenaga
  • Organizer: SfN2014
  • Place of Presentation: Washington D.C. , USA
  • Year and Date: 2014-11-15 – 2014-11-21
• [Presentation] Effects of 5-fluorouracil on stomatitis-induced pain in rats. (2014)
  • Author(s): K. Yamaguchi, N. Harano, S. Hitomi, K. Ono, S. Watanabe, K. Inenaga.
  • Organizer: SfN2014
  • Place of Presentation: Washington D.C. , USA
  • Year and Date: 2014-11-15 – 2014-11-21
• [Presentation] Acetaldehyde induces thirst sensation through the renin-angiotensin system in rats. (2014)
  • Author(s): I. Ujihara, S. Hitomi, K. Ono, Y. Kakinoki, K. Inenaga.
  • Organizer: SfN2014
  • Place of Presentation: Washington D.C. , USA
  • Year and Date: 2014-11-15 – 2014-11-21
• [Presentation] Tyrosinase-dependent peripheral dopamine production mediates pain sensitivity. (2014)
  • Author(s): K. Ono, C.T. Viet, D. Dang, Y. Ye and B.L. Schmidt.
  • Organizer: SfN2014
  • Place of Presentation: Washington D.C. , USA
  • Year and Date: 2014-11-15 – 2014-11-21
• [Presentation] ラット口内炎疼痛に対する半夏瀉心湯の効果 (2014)
  • Author(s): 人見涼露，小野堅太郎，山口喜一郎，寺脇潔，大宮雄司，金子篤，黒木愛由，宮野加奈子，上園保仁，稲永清敏
  • Organizer: 西日本生理学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-10-23 – 2014-10-24
• [Presentation] 二日酔い時の喉の渇きはアセトアルデヒドが原因で起こる (2014)
  • Author(s): 氏原泉、人見涼露、小野堅太郎、柿木保明、稲永清敏
  • Organizer: 西日本生理学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-10-23 – 2014-10-24
• [Presentation] 温度侵害受容特性は非ペプチド性無髄感覚神経のTrpv1発現により調節される (2014)
  • Author(s): 小野堅太郎、人見涼露、稲永清敏、Yi Ye、 Chi T. Viet、 Dongmin Dang、Brian L. Schmidt
  • Organizer: 西日本生理学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-10-23 – 2014-10-24
• [Presentation] 口内炎誘発疼痛に対する5-フルオロウラシルの影響 (2014)
  • Author(s): 山口喜一郎、人見涼露、小野堅太郎、原野望、左合徹平、渡邉誠之、稲永清敏
  • Organizer: 西日本生理学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-10-23 – 2014-10-24
• [Presentation] 口内炎疼痛に対する半夏瀉心湯の鎮痛効果 (2014)
  • Author(s): 人見涼露、小野堅太郎、寺脇潔、大宮雄司、金子篤、稲永清敏
  • Organizer: 第8回三叉神経感覚－運動統合機能研究会
  • Place of Presentation: 軽井沢
  • Year and Date: 2014-10-18 – 2014-10-19
• [Presentation] 抗ガン剤 ５-フルオロウラシルによる口内炎疼痛の増大 (2014)
  • Author(s): 小野堅太郎、山口喜一郎、人見涼露、稲永清敏
  • Organizer: 第8回三叉神経感覚－運動統合機能研究会
  • Place of Presentation: 軽井沢
  • Year and Date: 2014-10-18 – 2014-10-19
• [Presentation] 口内炎モデルラットに発症する口腔粘膜痛に対する半夏瀉心湯の効果 (2014)
  • Author(s): 人見涼露、小野堅太郎、稲永清敏
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 二日酔いでの口渇感はアセトアルデヒド誘発レニン・アンジオテンシン系の活性化により起こる (2014)
  • Author(s): 氏原泉、人見涼露、小野堅太郎、柿木保明、稲永清敏
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ラットにおける口内炎誘発疼痛に対する5-fluorouracilの影響 (2014)
  • Author(s): 山口喜一郎、人見涼露、小野堅太郎、原野望、左合徹平、稲永清敏
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 末梢ドーパミンの体色依存痛覚感受性における役割 (2014)
  • Author(s): 小野堅太郎、人見涼露、稲永清敏
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27