Hyperreactivity of thermo-sensitive TRP channel-expressing sensory neurons under stress conditions, and effects of herbal medicines on hyperesthesia

• Project/Area Number: 21590100
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Josai International University
• Principal Investigator: HORIE Syunji 城西国際大学, 薬学部, 教授 (50209285)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 薬効解析学 / 下部消化管 / TRPV1 / 消化管 / TRPA1 / 大建中湯 / セロトニン受容体 / 機能性胃腸症 / 炎症性腸疾患 / 知覚過敏性 / ストレス / 一酸化窒素 / 炎症 / カプサイシン / 免疫組織化学 / オピオイド受容体 / 神経ペプチド / 知覚過敏

Research Abstract

Psychological stress induces impairment of gastrointestinal tracts, leading to irritable bowel syndrome(IBS) accompanied by abdominal pain. The present study was designed with IBS model animals in order to elucidate the causes of IBS. As an important result, the stress induces the increased number of thermosensitive TRPV1-expressing nerve fibers, resulting in the hypersensitivity of visceral pain. Therefore, the inhibition of the abnormality of TRPV1 nerves in gut will make a contribution to the treatment of irritable bowel syndrome. I propose that Japanese Kampo medicine such as Daikenchuto will be a candidate that has the inhibitory effect of the abnormality on TRPV1 nerves in gut.

Research Products

• [Journal Article] Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice (2012)
  • Author(s): Matsumoto, K., Lo, Wah, M., Hosoya, T., Tashima, K., Takayama, H., Murayama, T., Horie, S
  • Journal Title: Laboratory Investigation Volume: 92(5) Pages: 769-782
  • Peer Reviewed
• [Journal Article] Subdiaphragmatic vagotomy induces a functional change in visceral Aδprimary afferent fibers in rats (2012)
  • Author(s): Furuta S, Matsumoto K, Horie S, Suzuki T, Narita M
  • Journal Title: Synapse Volume: 66(4) Pages: 369-371
  • Peer Reviewed
• [Journal Article] Dysfunction of neurogenic VIP-mediated relaxation in mouse distal colon with dextran sulfate sodium-induced colitis (2012)
  • Author(s): Kato E, Yamane, S, Nomura R, Matsumoto K, Tashima K, Horie S, Saito T, Fujino H, Murayama T
  • Journal Title: Pharmacological Research Volume: 65(2) Pages: 204-212
  • Peer Reviewed
• [Journal Article] Decrease of guanylyl cyclase SS 1 subunit and nitric oxide(NO)-induced relaxation in mouse rectum with colitis and its reproduction on long-term NO treatment (2012)
  • Author(s): Hamada Y, Kato E, Nakamura H, Fujino H, Matsumoto K, Tashima K, Horie S, Murayama T
  • Journal Title: Naunyn-Schmiedeberg Arch. Pharmacol Volume: 385(1) Pages: 81-94
  • Peer Reviewed
• [Journal Article] Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice (2012)
  • Author(s): Matsumoto, K., Lo, Wah, M., Hosoya, T., Tashima, K., Takayama, H., Murayama, T., Hone, S.
  • Journal Title: Laboratory Investigation Volume: 92 Issue: 5 Pages: 769-782
  • DOI: 10.1038/labinvest.2012.14
  • Peer Reviewed
• [Journal Article] Decrease of guanylyl cyclase β1 subunit and nitric oxide (NO)-induced relaxation in mouse rectum with colitis and its reproduction on long-term NO treatment (2012)
  • Author(s): Hamada Y, Kato E, Nakamura H, Fujino H, Matsumoto K, Tashima K, Horie S, Murayama T
  • Journal Title: Naunyn-Schmiedeberg Arch.Pharmacol. Volume: 385 Pages: 81-94
  • Peer Reviewed
• [Journal Article] Subdiaphragmatic vagotomy induces a functional change in visceral A-delta primary afferent fibers in rats (2012)
  • Author(s): Furuta S, Matsumoto K, Horie S, Suzuki T, Narita M
  • Journal Title: Synapse Volume: 66 Issue: 4 Pages: 369-371
  • DOI: 10.1002/syn.20991
  • Peer Reviewed
• [Journal Article] Distribution of transient receptor potential vanilloid 1 channel-expressing nerve fibers in mouse rectal and colonic enteric nervous system : relationship to peptidergic and nitrergic neurons (2011)
  • Author(s): Matsumoto, K., Hosoya, T., Tashima, K., Namiki, T., Murayama, T., Horie, S
  • Journal Title: Neuroscience Volume: 172 Pages: 518-534
  • Peer Reviewed
• [Journal Article] 迷走神経機能不全下での知覚神経感作とセロトニン4受容体作動薬mosaprideによる鎮痛効果 (2011)
  • Author(s): 古田貞由、松本健次郎、堀江俊治、鈴木勉、成田年
  • Journal Title: 日本緩和医療薬学雑誌 Volume: 4(3) Pages: 93-98
  • NAID: 40019043862
  • Peer Reviewed
• [Journal Article] ワサビ受容体TRPA1の胃機能における役割-バニロイド受容体TRPV1との比較- (2011)
  • Author(s): 田嶋公人、松本健次郎、堀江俊治
  • Journal Title: G. I. Research Volume: 19(3) Pages: 210-216
• [Journal Article] Inhibitory effect of Iboga-type indole alkaloids on capsaicin-induced contraction in isolated mouse rectum (2011)
  • Author(s): Lo, Wah, M. W., Matsumoto, K., Iwai, M., Tashima, K., Kitajima, M., Horie, S., Takayama, H
  • Journal Title: J. Nat. Med. Volume: 65(1) Pages: 157-165
  • Peer Reviewed
• [Journal Article] ワサビ受容体TRPA1の胃機能における役割-バニロイド受容体TRPV1との比較- (2011)
  • Author(s): 田嶋公人、松本健次郎、堀江俊治
  • Journal Title: G.I.Research Volume: 19 Pages: 210-216
• [Journal Article] Inhibitory effect of Iboga-type indole alkaloids on capsaicin-induced contraction in isolated mouse rectum (2011)
  • Author(s): Wah, L.M.
  • Journal Title: Journal of Natural Medicines Volume: 65 Pages: 157-165
  • Peer Reviewed
• [Journal Article] Neurogenic contraction of mouse rectum via the cyclooxygenase pathway : Change of PGE2-indueced contraction with dextran sulfate sodium-induced colitis (2010)
  • Author(s): Hamada, Y., Murakami, I., Katoh, E., Yamane, S., Fujino, H., Matsumoto, K., Tashima, K., Horie, S., Murayama, T
  • Journal Title: Pharmacological Research Volume: 61(1) Pages: 48-57
  • Peer Reviewed
• [Journal Article] Neurogenic contraction of mouse rectum via the cyclooxygenase pathway : Change of PGE2-indueced contraction with dextran sulfate sodium-induced colitis (2010)
  • Author(s): Hamada, Y.
  • Journal Title: Pharmacological Research Volume: 61 Pages: 48-57
  • Peer Reviewed
• [Journal Article] Neurogenic contraction of mouse rectum via the cyclooxygenase pathway : Change of PGE2-indueced contraction with dextran sulfate sodium-induced colitis (2010)
  • Author(s): Hamada, Y.
  • Journal Title: Pharmacological Research 61 Pages: 48-57
  • Peer Reviewed
• [Journal Article] Subdiaphragmatic vagotomy promotes nociceptive sensitivity of deep tissue in rats (2009)
  • Author(s): Furuta, S., Shimizu, T., Narita, M., Matsumoto, K., Kuzumaki, N., Horie, S., Suzuki, T., Narita, M
  • Journal Title: Neuroscience Volume: 164(3) Pages: 1252-1262
  • Peer Reviewed
• [Journal Article] Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine : high abundance and sensitivity in rectum and distal colon (2009)
  • Author(s): Matsumoto, K., Kurosawa, E., Terui, H., Hosoya, T., Tashima, K., Murayama, T., Priestley, J. V., Horie, S
  • Journal Title: Am. J. Physiol. Gastrointest. Liver Physiol Volume: 297(2)
  • Peer Reviewed
• [Journal Article] Nicotine-induced neurogenic relaxation in the mouse colon ; changes with dextran sodium sulfate-induced colitis (2009)
  • Author(s): Murakami I., 他4名
  • Journal Title: J. Pharmacol. Sci. Volume: 109(1) Pages: 128-138
  • Peer Reviewed
• [Journal Article] Nicotine-induced neurogenic relaxation in the mouse colon : changes with dextran sodium sulfate-induced colitis (2009)
  • Author(s): Murakami, I.
  • Journal Title: J.Pharmacol. Sci. 109 Pages: 128-138
  • Peer Reviewed
• [Journal Article] Subdiaphragmatic vagotomy promotes nociceptive sensitivity of deep tissue in rats. (2009)
  • Author(s): Furuta, S.
  • Journal Title: Neuroscience 164 Pages: 1252-1262
  • Peer Reviewed
• [Journal Article] Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine : high abundance and sensitivity in rectum and distal colon (2009)
  • Author(s): Matsumoto, K.
  • Journal Title: Am.J.Physiol. Gastrointest. Liver Physiol. 297
  • Peer Reviewed
• [Journal Article] 消化管におけるセロトニンシグナリングシステムと内臓知覚
  • Author(s): 堀江俊治、田嶋公人、松本健次郎
  • Journal Title: G. I. Research Volume: 18(5) Pages: 387-393
• [Presentation] Effect of allyl isothiocyanate, a dietary activator of TRPA1, on gastric mucosal defense mechanisms in rats : comparison with capsaicin (2011)
  • Author(s): Kimihito Tashima, Kenjiro Matsumoto, Syunji Horie
  • Organizer: International Symposium on Gastrointestinal Research
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2011-11-17
• [Presentation] 肺におけるバニロイド受容体とニューロキニンAとの関係 (2011)
  • Author(s): 渡邉直人、松本健次郎、田嶋公人、堀江俊治
  • Organizer: 第13回咳嗽研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-05
• [Presentation] トウガラシ辛味成分カプサイシンの麻酔下ラット胃粘膜血流増大作用: TRPV1神経線維に存在するNO合成酵素の関与 (2011)
  • Author(s): 堀江俊治、田嶋公人、松本健次郎
  • Organizer: 第13回日本神経消化器病学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-11-05
• [Presentation] トウガラシ辛味成分カプサイシンの麻酔下ラット胃粘膜血流増大作用:TRPV1神経線維に存在するNO合成酵素の関与 (2011)
  • Author(s): 堀江俊治、田嶋公人、松本健次郎
  • Organizer: 第13回日本神経消化器病学会
  • Place of Presentation: 栃木県総合文化センター(栃木県)
  • Year and Date: 2011-11-05
• [Presentation] 研究室に漢方医がやってきた:薬理学研究室の強みと弱み (2011)
  • Author(s): 堀江俊治、田嶋公人、松本健次郎、來村昌紀、奥見裕邦
  • Organizer: 第21回漢方治療研究会
  • Place of Presentation: 千葉
  • Year and Date: 2011-09-25
• [Presentation] 研究室に漢方医がやってきた:薬理学研究室の強みと弱み (2011)
  • Author(s): 堀江俊治
  • Organizer: 第21回漢方治療研究会
  • Place of Presentation: 千葉大学(千葉県)
  • Year and Date: 2011-09-25
• [Presentation] 麻酔下ラットにおけるワサビ辛味成分アリルイソチオシアネートによる胃粘膜傷害性と粘膜血流増大反応 (2011)
  • Author(s): 堀江俊治、佐藤翔吾、來村昌紀、松本健次郎、村山俊彦、並木隆雄、寺澤捷年、田嶋公人
  • Organizer: 第13回応用薬理シンポジウム
  • Place of Presentation: 日本大学(千葉県)
  • Year and Date: 2011-09-04
• [Presentation] 分泌型ホスホリパーゼA2の腸管自発性運動機能への影響と潰瘍性大腸炎モデル動物での変動解析 (2011)
  • Author(s): 野村涼也, 中村浩之, 藤野裕道, 堀江俊治, 村山俊彦
  • Organizer: 第124回日本薬理学会関東部会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-04
• [Presentation] トウガラシの辛味は胃腸でも味わう:胃におけるバニロイド受容体TRPV1の分布と機能 (2011)
  • Author(s): 堀江俊治、田嶋公人、松本健次郎
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: グランシップ(静岡県)
  • Year and Date: 2011-03-29
• [Presentation] マウス大腸におけるTRPM8チャネルの局在とTRPM8作動薬の平滑筋作用 (2011)
  • Author(s): 細谷拓司、松本健次郎、田嶋公人、村山俊彦、堀江俊治
  • Organizer: 第84回日本薬理学会
  • Place of Presentation: 横浜
• [Presentation] トウガラシの辛味は胃腸でも味わう:胃におけるバニロイド受容体TRPV1の分布と機能 (2011)
  • Author(s): 堀江俊治、田嶋公人、松本健次郎
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] Immunohistochemical analysis of altered serotonin signaling and transient receptor potential vanilloid 1 channels in experimental colitis mice (2011)
  • Author(s): Kenjiro Matsumoto, Kimihito Tashima, Syunji Horie
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago, USA
• [Presentation] Role of neuronal and non-neuronal transient receptor potential vanilloid type 1 and sensory neuropeptides in DSS-induced peripheral inflammatory changes (2011)
  • Author(s): Kenjiro Matsumoto, Takuji Hosoya, Kenta Kijiyama, Rikako Suzuki, Kimihito Tashima, Toshihiko Murayama, Syunji Horie
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago, USA
• [Presentation] Distribution of transient receptor potential vanilloid 1 channels-expressing nerve fibers in mouse lower esophageal sphincter (2011)
  • Author(s): Kenjiro Matsumoto, Rikako Suzuki, Eriko Ishikawa, Kenta Kijiyama, Syunji Horie
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago, USA
• [Presentation] A Dietary Agonist of TRPV1 Inhibits Gastric Acid Secretion and Increases Gastric Mucosal Blood Flow in Mice (2011)
  • Author(s): Hirokuni Okumi, Tetsuya Takeuchi, Kimihito Tashima, Kenjiro Matsumoto, Takao Namiki, Syunji Horie
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago, USA
• [Presentation] Allyl Isothiocyanate, a Dietary Activator of TRPA1, Increases Gastric Mucosal Blood Flow Through TRPV1-Expressing and Non-Expressing Sensory Nerves in Rats (2011)
  • Author(s): Kimihito Tashima, Masatoshi Yoshikubo, Masaki Raimura, Kenya Ozone, Hirokuni Okumi, Kenjiro Matsumoto, Atsushi Chino, Takao Namiki, Syunji Horie
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago, USA
• [Presentation] 成因の異なる3種類の内臓痛覚過敏モデルラットにおける大建中湯および小建中湯の改善作用 (2011)
  • Author(s): 松本健次郎、堀江俊治
  • Organizer: 第28回和漢医薬学会学術大会
  • Place of Presentation: 富山
• [Presentation] 麻酔下ラットにおけるワサビ辛味成分アリルイソチオシアネートによる胃粘膜傷害性と粘膜血流増大反応 (2011)
  • Author(s): 堀江俊治、佐藤翔吾、來村昌紀、松本健次郎、村山俊彦、並木隆雄、寺澤捷年、田嶋公人
  • Organizer: 第13回応用薬理シンポジウム
  • Place of Presentation: 船橋
• [Presentation] アフリカ伝承民間薬成分voacangineは天然由来のTRPV1アンタゴニストである (2011)
  • Author(s): 寺田祐子、堀江俊治、高山廣光、佐藤努、渡辺達夫
  • Organizer: 第26回日本香辛料研究会
  • Place of Presentation: 福井
• [Presentation] トウガラシの辛味は胃腸でも味わう-カプサイシン受容体TRPV1の消化管分布と消化管疾患- (2010)
  • Author(s): 堀江俊治
  • Organizer: 一般用医薬品・植物製剤の現状と将来研究会
  • Place of Presentation: 東京・日本薬学会永井記念会館(招待講演)
  • Year and Date: 2010-11-26
• [Presentation] トウガラシ辛味成分カプサイシンの麻酔下ラット胃粘膜血流増大作用における神経型NO合成酵素の関与.(静岡、2010.11.11-12) (2010)
  • Author(s): 堀江俊治
  • Organizer: 第25回日本香辛料研究会
  • Place of Presentation: 静岡・静岡県立大学
  • Year and Date: 2010-11-11
• [Presentation] 麻酔下ラットにおけるワサビ辛味成分アリルイソチオシアネートの胃粘膜傷害性とそれに対する粘膜防御反応 (2010)
  • Author(s): 堀江俊治
  • Organizer: 第25回日本香辛料研究会
  • Place of Presentation: 静岡・静岡県立大学
  • Year and Date: 2010-11-11
• [Presentation] トウガラシの辛味は胃腸でも味わう:消化管疾患とカプサイシン受容体 (2010)
  • Author(s): 堀江俊治
  • Organizer: フォーラム富山「創薬」第31回研究会
  • Place of Presentation: 富山・名鉄トヤマホテル(招待講演)
  • Year and Date: 2010-05-18
• [Presentation] Effect of Allyl Isothiocyanate, A Pungent Ingredient of Wasabi and Mustard Oil, on Gastric Mucosal Blood Flow and Ulcerogenesis in Rats : Comparison with Capsaicin (2010)
  • Author(s): Tashima K.
  • Organizer: Digestive Disease Week 2010
  • Place of Presentation: ニューオーリンズ・USA
• [Presentation] Distribution of transient receptor potential vanilloid(TRPV) 1 channels-expressing nerve fibers in mouse rectal and colonic enteric nervous system : relationship to peptidergic and nitrergic neurons and interstitial cells of Cajal(ICC) (2010)
  • Author(s): Matsumoto K.
  • Organizer: Digestive Disease Week 2010
  • Place of Presentation: ニューオーリンズ・USA
• [Presentation] Relaxatory responses of mouse lower gastrointestinal tract mediated to transient receptor potential melastatin type-8 (TRPM8) channel activation (2010)
  • Author(s): Hosoya T.
  • Organizer: Digestive Disease Week 2010
  • Place of Presentation: ニューオーリンズ・USA
• [Presentation] Immunohistochemical characterisation of TRPV1-expressing nerve fibers and serotonin signalling in mouse rectum (2010)
  • Author(s): Lo M.W.
  • Organizer: Digestive Disease Week 2010
  • Place of Presentation: ニューオーリンズ・USA
• [Presentation] 麻酔下ラットにおけるワサビ辛味成分アリルイソチオシアネートによる胃粘膜傷害性と粘膜血流増大反応 (2010)
  • Author(s): 堀江俊治
  • Organizer: 第27回和漢医薬学会学術大会
  • Place of Presentation: 京都・京都薬科大学
• [Presentation] 麻酔下ラットへのワサビ辛味成分アリルイソチオシアネート胃内適用による粘膜障害性と粘膜血流増大 (2010)
  • Author(s): 田嶋公人
  • Organizer: 第6回日本消化管学会
  • Place of Presentation: 福岡
• [Presentation] マウス下部消化管におけるTRPV1発現神経の分布と神経ペプチド,セロトニン,NO合成酵素の局在に関する免疫組織学的検討 (2010)
  • Author(s): 松本健次郎
  • Organizer: 第6回日本消化管学会
  • Place of Presentation: 福岡
• [Presentation] 辛味は胃腸をととのえる:カプサイシン受容体TRPV1の消化管分布と機能 (2009)
  • Author(s): 堀江俊治
  • Organizer: 第53回日本薬学会関東支部大会
  • Place of Presentation: 埼玉
  • Year and Date: 2009-10-03
• [Presentation] ラット胃におけるバニロイド受容体TRPV1発現神経の分布:脳腸ペプチドおよび一酸化窒素合成酵素との共存 (2009)
  • Author(s): 堀江俊治
  • Organizer: 第24回日本香辛料研究会
  • Place of Presentation: 大阪
• [Presentation] ラット胃におけるバニロイド受容体transient receptor potential vanilloid subtype 1(TRPV1)発現神経の分布:神経型-酸化窒素合成酵素との共存 (2009)
  • Author(s): 堀江俊治
  • Organizer: 第37回日本潰瘍学会
  • Place of Presentation: 東京
• [Presentation] Immunolocalization of transient receptor potential vanilloid-1(TRPV1)channels in ratstomach : relationship to neuropeptides and nitric oxide (2009)
  • Author(s): Horie, S.
  • Organizer: 13th International Conference on Gastrointestinal Research and 13th International Conference on Ulcer Research
  • Place of Presentation: クロアチア・スプリット
• [Presentation] Allyl-isothiocyanate, a pungent ingredient of wasabi, impairs gastric paracellular barrier in primary cultures from the rat stomach via TRPA1-independent pathway (2009)
  • Author(s): Tashima, K.
  • Organizer: 13th International Conference on Gastrointestinal Research and 13th International Conference on Ulcer Research
  • Place of Presentation: クロアチア・スプリット
• [Book] スパイス・ハーブの機能と最新応用技術 (2011)
  • Author(s): 堀江俊治
  • Total Pages: 288
  • Publisher: シーエムシー出版
• [Book] 第10章ナス科植物(トウガラシ属)と機能カプサイシンの胃粘膜保護作用.スパイス・ハーブの機能と最新応用技術
  • Author(s): 堀江俊治、田嶋公人、松本健次郎
  • Publisher: シーエムシー出版
• [Patent(Industrial Property Rights)] オピオイド鎮痛剤 (2010)
  • Inventor(s): 高山廣光、北島満里子、堀江俊治、松本健次郎
  • Industrial Property Rights Holder: 高山廣光、北島満里子、堀江俊治、松本健次郎
  • Industrial Property Number: 2009-543879
  • Filing Date: 2010
• [Patent(Industrial Property Rights)] Indole alkaloid derivatives having opioid receptor agonistic effect, and therapeutic compositions and methods relating to same (2007)
  • Inventor(s): 高山廣光、北島満里子、堀江俊治、松本健次郎
  • Industrial Property Rights Holder: 高山廣光、北島満里子、堀江俊治、松本健次郎
  • Filing Date: 2007