Inflammasome mediated neuroinflammation as a novel target of chronic pain

• Project/Area Number: 15H04969
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Fumimasa Amaya 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60347466)
• Co-Investigator(Kenkyū-buntansha): 岡林 志帆子 京都府立医科大学, 医学部附属病院, 研究員 (00744898) ; 佐和 貞治 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10206013) ; 大橋 憲太郎 岐阜大学, 工学部, 准教授 (50332953) ; 澤田 麻衣子 京都府立医科大学, 医学(系)研究科(研究院), 助教 (90330860)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: インフラマソーム / 神経炎症 / 痛覚過敏 / 後根神経節

Outline of Final Research Achievements

The aim of this study was to investigate the hypothesis that activation of inflammasome in the DRG contributes to the development of chronic pain hypersensitivity.
NLRP2 expression and caspase1 activity was measured in DRG of chronic inflammation model mouse. Both NLRP2 expression and caspase1 activity was increased by chronic inflammation. Caspase1 inhibitor and NLRP2 siRNA reduced pain hypersensitivity during chronic inflammation.
These results demonstrated that NLRP2 inflammasome in the DRG contributes to the development of chronic inflammatory pain hypersensitivity.

Research Products

• [Journal Article] Synergistic activation of ERK1/2 between A-fiber neurons and glial cells in the DRG contributes to pain hypersensitivity after tissue injury. (2018)
  • Author(s): Yamakita S, Horii Y, Takemura H, Matsuoka Y, Yamashita A, Yamaguchi Y, Matsuda M, Sawa T, Amaya F
  • Journal Title: Mol Pain Volume: 14 Pages: 1-10
  • DOI: 10.1177/1744806918767508
  • Peer Reviewed / Open Access
• [Journal Article] Functional validation of ATF4 and GADD34 in Neuro2a cells by CRISPR/Cas9-mediated genome editing. (2018)
  • Author(s): Oh-hashi K, Sugiura N, Amaya F, Isobe KI, Hirata Y.
  • Journal Title: Mol Cell Biochem. Volume: 440 Issue: 1-2 Pages: 65-75
  • DOI: 10.1007/s11010-017-3156-0
  • Peer Reviewed
• [Journal Article] Dexmedetomidine prolongs levobupivacaine analgesia via inhibition of inflammation and p38 MAPK phosphorylation in rat dorsal root ganglion (2017)
  • Author(s): Yamakita Shunsuke、Matsuda Megumi、Yamaguchi Yosuke、Sawa Teiji、Amaya Fumimasa
  • Journal Title: Neuroscience Volume: 361 Pages: 58-68
  • DOI: 10.1016/j.neuroscience.2017.08.011
  • Peer Reviewed
• [Journal Article] Acquired Exchange Protein Directly Activated by Cyclic Adenosine Monophosphate Activity Induced by p38 Mitogen-activated Protein Kinase in Primary Afferent Neurons Contributes to Sustaining Postincisional Nociception (2017)
  • Author(s): Matsuda Megumi、Oh-hashi Kentaro、Yokota Isao、Sawa Teiji、Amaya Fumimasa
  • Journal Title: Anesthesiology Volume: 126 Issue: 1 Pages: 150-162
  • DOI: 10.1097/aln.0000000000001401
  • Peer Reviewed
• [Journal Article] Risk factors and prognosis of pain events during mechanical ventilation: a retrospective study (2017)
  • Author(s): Yamashita A, Yamasaki M, Matsuyama H, Amaya F
  • Journal Title: J Intensive Care Volume: 5 Issue: 1 Pages: 17-17
  • DOI: 10.1186/s40560-017-0212-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Application of NanoLuc to monitor the intrinsic promoter activity of GRP78 using the CRISPR/Cas9 system (2016)
  • Author(s): Oh-Hashi K, Furuta E, Norisada J, Amaya F, Hirata Y, Kiuchi K.
  • Journal Title: Genes Cells Volume: 10 Issue: 10 Pages: 1137-1143
  • DOI: 10.1111/gtc.12401
  • Peer Reviewed
• [Journal Article] Comparative Effects of Periarticular Multimodal Drug Injection and Single-Shot Femoral Nerve Block on Pain Following Total Knee Arthroplasty and Factors Influencing Their Effectiveness (2016)
  • Author(s): Nakagawa S, Arai Y, Inoue H, Kan H, Hino M, Ichimaru S, Ikoma K, Fujiwara H, Amaya F, Sawa T, Kubo T
  • Journal Title: Knee Surg Relat Res. Volume: 3 Issue: 3 Pages: 233-8
  • DOI: 10.5792/ksrr.2016.28.3.233
  • Peer Reviewed
• [Journal Article] Effective evaluation of arterial pulse waveform analysis by two-dimensional stroke volume variation-stroke volume index plots (2016)
  • Author(s): Sawa T, Kinoshita M, Kainuma A, Akiyama K, Naito Y, Kato H, Amaya F, Shigemi K
  • Journal Title: Journal of Clinical Monitoring and Computing Volume: 30 Issue: 5 Pages: 1-15
  • DOI: 10.1007/s10877-016-9916-7
  • Peer Reviewed / Open Access
• [Journal Article] Cellular Stress Responses and Monitored Cellular Activities. (2016)
  • Author(s): Sawa T, Naito Y, Kato H, Amaya F.
  • Journal Title: Shock Volume: 46 Issue: 2 Pages: 113-121
  • DOI: 10.1097/shk.0000000000000603
  • Peer Reviewed
• [Journal Article] A Comparative Analysis of the Molecular Features of MANF and CDNF (2016)
  • Author(s): Norisada J, Hirata Y, Amaya F, Kiuchi K, Oh-Hashi K
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0146923-e0146923
  • DOI: 10.1371/journal.pone.0146923
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cellular Stress Responses and Monitored Cellular Activities. (2016)
  • Author(s): Sawa T, Naito Y, Katoh H, Amaya F.
  • Journal Title: Shock Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Can acute pain treatment reduce postsurgical comorbidity after breast cancer surgery? A literature review. (2015)
  • Author(s): Amaya F, Hosokawa T, Okamoto A, Matsuda M, Yamaguchi Y, Yamakita S, Taguchi T, Sawa T.
  • Journal Title: Biomed Res Int. Volume: 2015 Pages: 641508-641508
  • DOI: 10.1155/2015/641508
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] mTOR signaling controls VGLUT2 expression to maintain pain hypersensitivity after tissue injury. (2015)
  • Author(s): Izumi Y, Sasaki M, Hashimoto S, Sawa T, Amaya F.
  • Journal Title: Neuroscience. Volume: 308 Pages: 169-179
  • DOI: 10.1016/j.neuroscience.2015.09.013
  • Peer Reviewed / Open Access
• [Presentation] Endogenous cannabinoids contribute to the resolution of incisional pain (2017)
  • Author(s): H. TAKEMURA, M. MATSUDA, F. AMAYA
  • Organizer: Society for Neuroscience annual meeting
  • Int'l Joint Research
• [Presentation] Expression of NLRP2 in the DRG and its regulation during inflammatory hyperalgesia (2017)
  • Author(s): Y. MATSUOKA, F. AMAYA
  • Organizer: Society for Neuroscience annual meeting
  • Int'l Joint Research
• [Presentation] Increased caspase1 activity in the DRG during inflammatory hyperalgesia (2016)
  • Author(s): Y. MATSUOKA, K. OH-HASHI, F. AMAYA
  • Organizer: Society for Neuroscience annual meeting 2016
  • Place of Presentation: 米国サンディエゴ
  • Int'l Joint Research
• [Presentation] EPAC is responsive for the exacerbation of the injury-induced pain hypersensitivity after the second surgery (2016)
  • Author(s): M. MATSUDA, F. AMAYA
  • Organizer: Society for Neuroscience annual meeting 2016
  • Place of Presentation: 米国サンディエゴ
  • Int'l Joint Research
• [Presentation] Bench to Bedsideレビュー：手術後に生じる知覚神経の機能変化 (2015)
  • Author(s): 天谷文昌
  • Organizer: 第2回日本区域麻酔学会学術集会
  • Place of Presentation: 高崎
  • Year and Date: 2015-04-25
  • Invited