Analysis of migraine pathophysiology in an animal model using small-animal PET

• Project/Area Number: 21600020
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 疼痛学
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: CUI Yilong 独立行政法人理化学研究所, 細胞機能イメージング研究チーム, 副チームリーダー (60312229)
• Co-Investigator(Kenkyū-buntansha): WATANABE Yasuyoshi 独立行政法人理化学研究所, 分子イメージング科学研究センター, センター長 (40144399)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: PET / 片頭痛 / 痛み / 脳内炎症 / 神経活動 / 脳機能画像解析 / 疼痛 / PETイメージング / 脳機能解剖学 / 神経回路

Research Abstract

Using in vivo PET imaging with FDG and[^<11> C] PK11195, a PET ligand for translocator protein(TSPO, previously called peripheral benzodiazepine receptor), we evaluated the pain matrix and neurogenic inflammatory process in the rat brain after generation of cortical spreading depression(SD), a stimulation used for making an experimental animal model of migraine. The results show that the uptake of[^<11> C] PK11195, which has been used extensively to image activated microglia in the central nervous system, in the unilateral SD model rats increased in the ipsilateral hemisphere, and completely displaced by excess unlabeled ligands. Moreover, a quantitative analysis showed the binding potential for[^<11> C] PK11195 to significantly increase in the ipsilateral hemisphere, suggesting a pathological role of microglia activation in migraine etiology. The results further show that the regional brain activity was significantly increased in several brain regions, including the ipsilateral brainstem, contralateral sensory, and insular cortex, which have been reported to be involved in a nociceptive pathway in migraine.

Research Products

• [Journal Article] Stoichiometry-focused^<18> F-labeling of alkyne-substituted oligodeoxynucleotides using azido([^<18> F] fluoromethyl) benzenes by Cu-catalyzed huisgen reaction (2011)
  • Author(s): Kuboyama, T., Nakahara, M., Yoshino, M., Cui, Y. L., Sako, T., Wada, Y., Imanishi, T., Obika, S., Watanabe, Y., Suzuki, M. and Doi, H.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 19 Pages: 249-255
  • Peer Reviewed
• [Journal Article] Imaging of gastrointestinal absorption process of orally administered drugs using positron emission tomography (2011)
  • Author(s): Yamashita, S., Takashima, T., Kataoka, M., Oh, H., Sakuma, S., Takahashi, M., Suzuki, N., Hayashinaka, E., Wada, Y., Cui, Y. L., and Watanabe, Y.
  • Journal Title: J Nucl Med Volume: 52 Pages: 249-256
  • Peer Reviewed
• [Journal Article] PET of Aromatase in Gastric Parietal Cells Using 11C-Vorozole (2011)
  • Author(s): Ozawa, M., Takahashi, K., Akazawa, K. H., Takashima, T., Nagata, H., Doi, H., Hosoya, T., Wada, Y., Cui, Y. L., Kataoka, Y. and Watanabe, Y.
  • Journal Title: J Nucl Med Volume: 52 Pages: 1964-1969
  • Peer Reviewed
• [Journal Article] 脳内炎症の分子イメージングと片頭痛病態 (2011)
  • Author(s): 崔翼龍、渡辺恭良、片岡洋祐
  • Journal Title: PETジャーナル Volume: 16(3) Pages: 14-16
• [Journal Article] Stoichiometry-focused ^<18>F-labeling of alkyne-substituted oligodeoxynucleotides using azido ([^<18>F]fluoromethyl) benzenes by Cu-catalyzed huis gen reaction (2011)
  • Author(s): Kuboyama, T., Nakahara, M., Yoshino, M., Cui, Y.L., Sako, T., Wada, Y., Imanishi, T., Obika, S., Watanabe, Y., Suzuki, M., Doi, H.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 19 Pages: 249-255
  • Peer Reviewed
• [Journal Article] 脳内炎症の分子イメージングと片頭痛病態 (2011)
  • Author(s): 崔翼龍、渡辺恭良、片岡洋祐
  • Journal Title: PET journal Volume: 16 Pages: 14-16
• [Journal Article] Stoichiometry-focused ^<18> F-labeling of alkyne-substituted oligodeoxynucleotides using azido ([^<18>F]fluoromethyl) benzenes by Cu-catalyzed huisgen reaction. (2011)
  • Author(s): Kuboyama, T., Nakahara, M., Yoshino, M., Cui, Y.L., Sako, T., Wada, Y., Imanishi, T., Obika,' S., Watanabe, Y., Suzuki, M., Doi, H.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 19 Pages: 249-255
  • Peer Reviewed
• [Journal Article] Mapping of regional brain activation in response to fatigue-load and recovery in rats with c-Fos immunohistochemistry (2010)
  • Author(s): Akazawa, K. H., Cui, Y. L., Tanaka, M., Kataoka, Y., Yoneda, Y., and Watanabe, Y.
  • Journal Title: Neurosci Res Volume: 66(4) Pages: 372-9
  • Peer Reviewed
• [Journal Article] PET studies using 15R-[11C] TIC-Me for the evaluation of hepatobiliary transport (2010)
  • Author(s): Takashima, T., Nagata, H., Nakae, T., Cui, Y. L., Wada, Y., Kitamura, S., Doi, H., Suzuki, M., Maeda, K., Kusuhara, H., Sugiyama, Y., and Watanabe, Y.
  • Journal Title: J Pharmacol Exp Ther Volume: 335(2) Pages: 314-323
  • Peer Reviewed
• [Journal Article] Mapping of regional brain activation in response to fatigue-load and recovery in rats with c-Fos immunohistochemistry (2010)
  • Author(s): Akazawa, K.H., Cui, Y.L., Tanaka, M., Kataoka, Y., Yoneda, Y., Watanabe, Y
  • Journal Title: Neurosci Res Volume: 66 Pages: 372-379
  • Peer Reviewed
• [Journal Article] 11C-PK11195 PET for the In Vivo Evaluation of Neuroinflammation in the Rat Brain After Cortical Spreading Depression (2009)
  • Author(s): Cui, Y. L., Takashima, T., Takashima-Hirano, M., Wada, Y., Shukuri, M., Tamura, Y., Doi, H., Onoe, H., Kataoka, Y. and Watanabe, Y
  • Journal Title: J Nucl Med Volume: 50(11) Pages: 1904-11
  • Peer Reviewed
• [Journal Article] 11C-PK11195 PET for the In Vivo Evaluation of Neuroinflammation in the Rat Brain After Cortical Spreading Depression (2009)
  • Author(s): Cui, Y.L.
  • Journal Title: J Nucl Med 50 Pages: 1904-11
  • Peer Reviewed
• [Journal Article] tron emission tomography (PET) imaging-based evaluation of hepatobiliary transport in humans using 15R-[^<11>C]TIC-Me
  • Author(s): Takashima, T., Kitamura, S., Wada, Y., Tanaka, M., Shigihara, Y., Ishii, H., Ijuin, R., Shiomi, S., Nakae, T., Watanabe, Y., Cui, Y.L., Doi, H., Suzuki, M., Maeda, K., Kusuhara, H., Sugiyama, Y., Watanabe, Y.
  • Journal Title: J Nucl Med Volume: 11(in press)
  • Peer Reviewed
• [Presentation] Visualizing neuroinflammation and the pain matrix in a migraine model rat using small-animal PET (2012)
  • Author(s): Cui, Y. L
  • Organizer: The 14th Conference of Peace through Mind/Brain Science
  • Place of Presentation: Hamamatsu Japan
  • Year and Date: 2012-02-15
• [Presentation] Visualizing neuroinflammation and the pain matrix in a migraine model rat using small-animal PET (2012)
  • Author(s): 崔翼龍
  • Organizer: The 14th Conference of Peace through Mind Brain Science
  • Place of Presentation: ホテルクラウンパレス浜松(浜松)(招待講演)
  • Year and Date: 2012-02-15
• [Presentation] MicroPETを用いたラット脳内の疼痛認知・伝達回路の解析 (2011)
  • Author(s): 崔翼龍,佐古健生,奥山香里,豊田浩士,尾上嘉代,林中恵美,和田康弘,渡辺恭良,片岡洋祐
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-16
• [Presentation] MicroPETを用いたラット脳内の疼痛伝達・認知回路の解析 (2011)
  • Author(s): 崔翼龍
  • Organizer: 第34回日本神経学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-09-16
• [Presentation] 脳内炎症の分子イメージングと片頭痛病態 (2011)
  • Author(s): 崔翼龍、高島忠之、高島好聖、佐古健生、奥山香里、林中恵美、和田康弘、土居久志、渡辺恭良、片岡洋祐
  • Organizer: 第6回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2011-05-26
• [Presentation] 脳内炎症の分子イメージングと片頭痛病態 (2011)
  • Author(s): 崔翼龍
  • Organizer: 第6回日本分子イメージング学会
  • Place of Presentation: 神戸国際会議場(神戸市)
  • Year and Date: 2011-05-26
• [Presentation] Mapping of regional brain activation in response to fatigue-load and recovery in rats with c-Fos immunohistochemistry (2010)
  • Author(s): Akazawa, K. H., Cui, Y. L., Tanaka, M., Kataoka, Y., Yoneda, Y., and Watanabe, Y
  • Organizer: Society for Neuroscience 40th Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-17
• [Presentation] PET imaging of neurogenic inflammation with[11C] PK11195 in the rat model of migraine (2010)
  • Author(s): Cui Y. L. Takashima M., Tadayuki, T., Okuyama K., Shukuri M., Hayashinaka E., Wada Y., Doi H., Onoe H., Watanabe Y., Kataoka Y.
  • Organizer: 2010 World Molecular Imaging Congress
  • Place of Presentation: Kyoto Japan
  • Year and Date: 2010-09-09
• [Presentation] PET imaging of neurogenic inflammation with [11C]PK11195 in the rat model of migraine (2010)
  • Author(s): Cui Y.L., Takashima M., Tadayuki, T., Okuyama K., Shukuri M., Hayashinaka E., Wada Y., Doi H., Onoe H., Watanabe Y., Kataoka Y
  • Organizer: 2010 World Molecular Imaging Congress
  • Place of Presentation: Kyoto
  • Year and Date: 2010-09-09
• [Presentation] 片頭痛病態モデルラットを用いた疼痛伝達回路の解析 (2010)
  • Author(s): 崔翼龍,佐古健生,豊田浩士,奥山香里,尾上嘉代,林中恵美,和田康弘,渡辺恭良,片岡洋祐
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-04
• [Presentation] 片頭痛病態モデルラットを用いた疼痛伝達回路の解析 (2010)
  • Author(s): 崔翼龍, 佐古健生, 豊田浩士, 奥山香里, 尾上嘉代, 林中恵美, 和田康弘, 渡辺恭良, 片岡洋祐
  • Organizer: 第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-04
• [Presentation] Pathophysiology of migrane studied with small-animal PET (2010)
  • Author(s): Cui Y. L.
  • Organizer: The thirteenth Conference of Peace through Mind/Brain Science
  • Place of Presentation: Hamamatsu Japan
  • Year and Date: 2010-02-24
• [Presentation] Pathophysiology of migrane studied with small-animal PET (2010)
  • Author(s): Cui Y.L
  • Organizer: The thirteenth Conference of Peace through Mind/Brain Science
  • Place of Presentation: Hamamatsu
  • Year and Date: 2010-02-24
• [Presentation] Pathophysiology of migrane studied with small-animal PET (2010)
  • Author(s): 崔翼龍
  • Organizer: The Thirteenth Conference of Peace through Mind/Brain Science
  • Place of Presentation: (浜松名鉄ホテル)浜松
  • Year and Date: 2010-02-24
• [Presentation] 片頭痛病態モデル動物におけるオピオイド受容体のPETイメージング (2010)
  • Author(s): 崔翼龍,長田浩子,佐古健生,奥山香里,尾上嘉代,豊田浩士,林中恵美,和田康弘,土居久志,渡辺恭良,片岡洋祐
  • Organizer: 分子イメージング研究シンポジウム2010「未来を拓く創薬・疾患診断研究」
  • Place of Presentation: 東京
  • Year and Date: 2010-01-20
• [Presentation] Palladium(0)-Mediated Rapid C-[11C] Methylation using an Organoboron Precursor :[11C] Celecoxib Synthesis and the Rat PET Imaging (2009)
  • Author(s): Doi H., Takashima M., Cui Y. L., Takashima T., Hayashinaka E., Wada Y., Watanabe Y., and Suzuki M.
  • Organizer: The 11th International Kyoto Conference on New Aspects of Organic Chemistry
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-11-12
• [Presentation] MicroPETを用いた片頭痛病態の解析 (2009)
  • Author(s): 崔翼龍、高島忠之、尾上嘉代、宿里充穂,高島好聖、佐古健生、林中恵美、和田康弘、土居久志、尾上浩隆、渡辺恭良、片岡洋祐
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-18
• [Presentation] MicroPETを用いた片頭痛病態の解析 (2009)
  • Author(s): 崔翼龍
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: (名古屋国際会議場)名古屋
  • Year and Date: 2009-09-18
• [Presentation] Neural and Molecular Mechanisms of Central Fatigue in the Animal Models (2009)
  • Author(s): Cui Y. L., Watanabe Y., and Kataoka Y.
  • Organizer: 36th Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-08-01
• [Presentation] Highly efficient synthesis of[11C] Celecoxib by Palldium(0)-mediated rapid C-[11C] methylation using an organoboron precursor and PET imaging of COX-2 expression in rat brains (2009)
  • Author(s): Takashima M., Cui Y. L., Takashima T., Hayashinaka E., Wada Y., Watanabe Y., Doi H., and Suzuki M.
  • Organizer: 18th International Symposium on Radiopharmaceutical Sciences
  • Place of Presentation: Edmonton, Canada
  • Year and Date: 2009-07-13