Effects of resolvins and their mechanism of action on the sensory and emotional components of pain

• Project/Area Number: 15K08670
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Kyoto University
• Principal Investigator: Satoh Masamichi 京都大学, 薬学研究科, 名誉教授 (80025709)
• Co-Investigator(Kenkyū-buntansha): 井手 聡一郎 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (30389118) ; 人羅 菜津子 北海道大学, 薬学研究院, 助教 (40762191)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: レゾルビン / 痛み / 抑うつ / 不安 / 不快情動 / ω-3系脂肪酸 / ω-3 系脂肪酸 / 慢性疼痛 / 抗うつ / mTOR / 炎症 / 多価不飽和脂肪酸 / LPS

Outline of Final Research Achievements

We investigated the effects of resolvins, metabolites of ω-3 fatty acids, on depression and anxiety symptoms associated with chronic pain. The intracerebroventricular administration of resolvin D1 (RvD1), D2 (RvD2), El (RvE1), and E2 (RvE2) demonstrated antidepressant effects in LPS-induced depression model mice. It was suggested that antidepressant effect of RvD1 is mediated through PI3K-mTOR pathway and MEK / ERK-mTOR pathway, and that antidepressant action of RvD2 is mediated by MEK / ERK-mTOR pathway. It was also suggested that the antidepressant effect of RvE1 is mediated through the ChemR23-mTOR pathway. Furthermore, in the chronic pain (SNI) model mouse, intracerebroventricular administration of Chemerin, an agonist of RvE1 or ChemR23, showed antidepressant effects. These results suggest that resolvins could improve the depressive symptoms caused by pain.

Research Products

• [Journal Article] M. Minami, Resolvin E1 and E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23 (2017)
  • Author(s): K. Deyama, Y. Shimoda, K. Ishikawa, H. Ishimura, H. Fukuda, S. Ide, M. Satoh, S. Shuto
  • Journal Title: Psychopharmacology Volume: 235 Issue: 1 Pages: 329-336
  • DOI: 10.1007/s00213-017-4774-7
  • Peer Reviewed
• [Journal Article] Rapid and sustained antidepressant effects of resolvin D1 and D2 in a chronic unpredictable stress model (2017)
  • Author(s): Ishikawa Yuka、Deyama Satoshi、Shimoda Kento、Yoshikawa Kotomi、Ide Soichiro、Satoh Masamichi、Minami Masabumi
  • Journal Title: Behav Brain Res. Volume: 332 Pages: 233-236
  • DOI: 10.1016/j.bbr.2017.06.010
  • Peer Reviewed
• [Journal Article] Resolvin D1 and D2 reverse lipopolysaccharide-induced depression-like behaviors through the mTORC1 signaling pathway. (2017)
  • Author(s): Deyama, S., Ishikawa, Y., Yoshikawa, K., Shimoda, K., Ide, S., Satoh, M., Minami, M.
  • Journal Title: Int. J. Neuropsychopharmacol. Volume: 印刷中 Issue: 7 Pages: 575-584
  • DOI: 10.1093/ijnp/pyx023
  • NAID: 120006355755
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] レゾルビンE1およびレゾルビンE2の抗うつ作用機序 (2018)
  • Author(s): 鈴木 博惠、出山 諭司、霜田 健斗、石川 由香、石村 航平、福田 隼、人羅（今村） 菜津子、井手 聡一郎、佐藤 公道、金田 勝幸、周東 智、南 雅文
  • Organizer: 日本薬学会 第138年会
• [Presentation] レゾルビンD1、D2の抗うつ作用メカニズムの解明 (2016)
  • Author(s): 石川由香、出山諭司、吉川琴美、霜田健斗、井手聡一郎、人羅（今村）菜津子、佐藤公道、南雅文
  • Organizer: 第38回日本生物学的精神医学会、第59回日本神経化学会大会
  • Place of Presentation: 福岡国際会議場