Novel enhancement mechanisms of the nociceptive response by serum exosomes in a mouse model of neuropathic pain

• Project/Area Number: 15H06795
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Applied health science
• Research Institution: Daiichi University, College of Pharmaceutical Sciences
• Principal Investigator: Hamamura Kengo 第一薬科大学, 薬学部, 助教 (30756466)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: エクソソーム / 神経障害性疼痛 / ホルマリン誘発性侵害刺激行動 / 疼痛

Outline of Final Research Achievements

Exosomes are small (40-150nm) membrane vesicles of endocytic origin that are found in blood and so on. Although various biomarkers in the serum exosomes are identified by recent studies, the influences of exosomes on pain are not elucidated. The objective of this study was to identify the relationship between serum exosomes in mice with partial sciatic nerve ligation (PSL) and alterations of nociceptive responses induced by formalin.
First, we have confirmed that the intrathecal injection of serum exosomes in mice with PSL into the normal mice did not produce spontaneous nociceptive response. However, 0.5% formalin-induced nociceptive response was enhanced significantly by serum exosomes obtained from PSL mice. In addition, surface protein "shaved" exosomes were ineffective on formalin-induced response. Taken together, our data indicate that the surface protein of exosomes in mice with PSL may play an important role in enhancing formalin-induced nociceptive responses.

Research Products

• [Journal Article] The involvement of spinal release of histamine on nociceptive behaviors induced by intrathecally administered spermine. (2017)
  • Author(s): Mizoguchi H, Watanabe C, Hayashi T, Iwata Y, Watanabe H, Katsuyama S, Hamamura K, Sakurada T, Ohtsu H, Yanai K, Sakurada S.
  • Journal Title: European Journal of Pharmacology Volume: 800 Pages: 9-15
  • DOI: 10.1016/j.ejphar.2017.01.031
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease. (2016)
  • Author(s): Matsunaga N, Ikeda E, Kakimoto K, Watanabe M, Shindo N, Tsuruta A, Ikeyama H, Hamamura K, Higashi K, Yamashita T, Kondo H, Yoshida Y, Matsuda M, Ogino T, Tokushige K, Itcho K, Furuichi Y, Nakao T, Yasuda K, Doi A, Amamoto T, Aramaki H, Tsuda M, Inoue K, Ojida A, Koyanagi S, Ohdo S
  • Journal Title: EBioMedicine Volume: 13 Pages: 262-273
  • DOI: 10.1016/j.ebiom.2016.10.008
  • Peer Reviewed / Open Access
• [Journal Article] Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction. (2016)
  • Author(s): Hamamura K, Matsunaga N, Ikeda E, Kondo H, Ikeyama H, Tokushige K, Itcho K, Furuichi Y, Yoshida Y, Matsuda M, Yasuda K, Doi A, Yokota Y, Amamoto T, Aramaki H, Irino Y, Koyanagi S, Ohdo S.
  • Journal Title: The Journal of Biological Chemistry Volume: 291 Issue: 10 Pages: 4913-4927
  • DOI: 10.1074/jbc.m115.696930
  • Peer Reviewed
• [Journal Article] Circadian Clock in a Mouse Colon Tumor Regulates Intracellular Iron Levels to Promote Tumor Progression. (2016)
  • Author(s): Okazaki F, Matsunaga N, Okazaki H, Azuma H, Hamamura K, Tsuruta A, Tsurudome Y, Ogino T, Hara Y, Suzuki T, Hyodo K, Ishihara H, Kikuchi H, To H, Aramaki H, Koyanagi S, Ohdo S
  • Journal Title: The Journal of biological chemistry Volume: 291 Issue: 13 Pages: 7017-7028
  • DOI: 10.1074/jbc.m115.713412
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mitomycin C modulates the circadian oscillation of clock gene period 2 expression through attenuating the glucocorticoid signaling in mouse fibroblasts. (2015)
  • Author(s): Kusunose N, Matsunaga N, Kimoto K, Akamine T, Hamamura K, Koyanagi S, Ohdo S, Kubota T.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 467 Issue: 1 Pages: 157-163
  • DOI: 10.1016/j.bbrc.2015.09.086
  • Peer Reviewed / Open Access
• [Presentation] Serum exosomes in a mouse model of neuropathic pain enhance the formalin-induced nociceptive response (2016)
  • Author(s): Kengo Hamamura, Naoki Kusunose, Soh Katsuyama, Takaaki Komatsu, Tsukasa Sakurada
  • Organizer: 16th World Congress on Pain
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] 神経障害性モデルマウスの血清中エクソソームは低濃度ホルマリン誘発侵害刺激行動を増強する (2016)
  • Author(s): 濵村 賢吾, 楠瀬 直喜, 勝山 壮, 小松 生明, 櫻田 司
  • Organizer: 第36回 鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2016-08-19
• [Presentation] 神経障害性モデルマウスの血清中エクソソームは低濃度ホルマリン 誘発侵害刺激行動を増強する (2016)
  • Author(s): 居石 奈菜美, 濵村 賢吾, 楠瀬 直喜, 勝山 壮, 西村 友里, 古川 翔太, 田中 大晴, 力久 諒派, 荒牧 弘範, 小松 生明, 櫻田 司
  • Organizer: 医療薬学フォーラム2016/第24回クリニカルファーマシーシンポジウム
  • Place of Presentation: 滋賀県大津市
  • Year and Date: 2016-06-25
• [Book] 体内時計分子機構と外的要因が耐糖能日周リズムを形成する (2015)
  • Author(s): 濵村賢吾
  • Total Pages: 2
  • Publisher: 公益社団法人 日本薬学会の学会誌「ファルマシア」, 2015年12月号