Mechanisms of pain sensation through interactions between TRP channels and anoctamin 1

• Project/Area Number: 15K19197
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pain science
• Research Institution: Okazaki Research Facilities, National Institutes of Natural Sciences
• Principal Investigator: TAKAYAMA Yasunori 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 特任助教 (60711033)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: TRPV1 / アノクタミン1 / 疼痛 / 一次感覚神経 / 急性疼痛

Outline of Final Research Achievements

TRPV1, a capsaicin receptor, is an important ion channel in sensory nerves to detect painful situation in skin. For long time, TRPV1 has been believed as main ion channel inducing burning pain, however we identified the interaction with anoctamin 1, a kind of chloride channel. This TRPV1-anoctamin 1 interaction is a molecular mechanism to enhance TRPV1-mediated pain sensation. In addition, capsaicin-induced pain was reduced by anoctamin 1 inhibitor. Thus, the painkiller targeting anoctamin 1 could be better therapy in clinical situations.
Furthermore, we found a new chemical compound which has inhibitory effect on anoctamin 1 activity. Therefore, this chemical could be novel seeds in the development of painkiller.

Research Products

• [Journal Article] 4-isopropylcyclohexanol has potential analgesic effects through the inhibition of anoctamin 1, TRPV1 and TRPA1 channel activities. (2017)
  • Author(s): Takayama Y, Furue H, Tominaga M.
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 43132-43132
  • DOI: 10.1038/srep43132
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation. (2016)
  • Author(s): Yoshida A, Furube E, Mannari T, Takayama Y, Kittaka H, Tominaga M, Miyata S
  • Journal Title: Sci Rep. Volume: 18 Issue: 1 Pages: 26088-26088
  • DOI: 10.1038/srep26088
  • Peer Reviewed / Open Access
• [Journal Article] Infantile pain episodes associated with novel Nav1.9 mutations in familial episodic pain syndrome in Japanese families (2016)
  • Author(s): Hiroko Okuda, Atsuko Noguchi, Hatasu Kobayashi, Daiki Kondo, Kouji H.Harada, Shohab Youssefian, Hirotomo Shioi, Risako kabata, Yuki Domon,Kazufumi Kubota, Yutaka Kitano, Yasunori Takayama, Toshiaki Hitomi,Kousaku Ohno, Yoshiaki Saito, Takeshi Asano, Makoto Tominaga, Tsutomu Takahashi, and Akio Koizumi.
  • Journal Title: PLOS ONE Volume: 11 Issue: 5 Pages: e0154827-e0154827
  • DOI: 10.1371/journal.pone.0154827
  • NAID: 120005946996
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lack of TRPV2 impaired thermogenesis in mouse brown adipose tissue. (2016)
  • Author(s): 1.Sun, W., Uchida, K., Suzuki, Y., Zhou, Y., Kim, M., Takayama, Y., Takahashi, N., Goto, T., Wakabayashi, S., Kawada, T., Iwata, Y., and Tominaga, M
  • Journal Title: EMBO Report Volume: 17 Issue: 3 Pages: 383-399
  • DOI: 10.15252/embr.201540819
  • Peer Reviewed / Open Access
• [Journal Article] Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons (2015)
  • Author(s): Takayama Y, Uta D, Furue H, Tominaga M
  • Journal Title: Proceedings of the National Academy of Sciences of the U S A. Volume: 112(16) Issue: 16 Pages: 5213-8
  • DOI: 10.1073/pnas.1421507112
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Interaction of TRPV1 and ANO1 in DRG neurons (2016)
  • Author(s): Takayama Y, Tominaga M
  • Organizer: International Association for the Study of Pain
  • Place of Presentation: 神奈川, 横浜, パシフィコ横浜
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Interaction of transient receptor potential vanillin 1 and anoctamin 1 in primary sensory neurons (2016)
  • Author(s): Takayama Y, Tominaga M
  • Organizer: Physiology 2016
  • Place of Presentation: アイルランド, ダブリン, Convention Centre
  • Year and Date: 2016-07-29
  • Int'l Joint Research
• [Presentation] DRGニューロンにおけるTRPV1-ANO1相互作用とメントールによるANO1阻害効果の検討 (2016)
  • Author(s): 高山 靖規，秋元 望，古江 秀昌，富永 真琴
  • Organizer: 第38回 日本疼痛学会
  • Place of Presentation: 北海道, 札幌, 北海道立道民活動センター かでる2・7
  • Year and Date: 2016-06-24
• [Presentation] Does TRPV1-ANO1 interaction enhance HOT taste ? (2016)
  • Author(s): Takayama Y, Tominaga M
  • Organizer: International Symposium on Olfaction and Taste
  • Place of Presentation: 神奈川, 横浜, パシフィコ横浜
  • Year and Date: 2016-06-05
  • Int'l Joint Research
• [Presentation] Investigation of ANO1 blocker and the effect on TRPV1-related pain (2016)
  • Author(s): Yasunori Takayama, Nozomi Akimoto, Hidemasa Furue, Makoto Tominaga
  • Organizer: 第93回 日本生理学会大会
  • Place of Presentation: 北海道, 札幌, 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] Menthol effects on ANO1 currents and TRPV1-related pain (2015)
  • Author(s): 高山 靖規，秋元 望，古江 秀昌，富永 真琴
  • Organizer: 生理学研究所 研究会「痛みの理解を目指した先端的アプローチ」
  • Place of Presentation: 愛知, 岡崎, 岡崎カンファレンスセンター
  • Year and Date: 2015-12-17
• [Presentation] TRPV1-ANO1 interaction in sensory neurons (2015)
  • Author(s): Yasunori Takayama, Makoto Tominaga
  • Organizer: TRP 2015
  • Place of Presentation: ベルギー, ルーベン
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] Inhibition of anoctamin 1-mediated currents by menthol (2015)
  • Author(s): Yasunori Takayama, Makoto Tominaga
  • Organizer: 第38回 日本神経科学大会
  • Place of Presentation: 兵庫, 神戸, 神戸国際会議場
  • Year and Date: 2015-07-28
• [Remarks] 新たな鎮痛薬創薬シーズの発見
  • URL: http://www.nips.ac.jp/release/2017/02/_4-.html
• [Remarks] カプサイシンが引き起こす痛みの増強メカニズム
  • URL: http://www.nips.ac.jp/release/2015/04/_trpv1.html
• [Patent(Industrial Property Rights)] 活性抑制剤および皮膚感覚過敏抑制剤 (2017)
  • Inventor(s): 高山 靖規, 富永 真琴
  • Industrial Property Rights Holder: 大学共同利用機関法人自然科学研究機構
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017-02-08