Therapeutic possibility of MANF, a new class of nerve growth factor, against neuropathic pain.

• Project/Area Number: 26670692
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Amaya Fumimasa 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): 大橋 憲太郎 岐阜大学, 工学部, 准教授 (50332953)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 小胞体ストレス / MANF / SNL / ERストレス / 痛覚過敏

Outline of Final Research Achievements

MANF is induced by ER stress and acts protectively in the hippocampus. In this analysis, we investigated the expression of MANF and pain hypersensitivity after the peripheral nerve injury. Rats were treated with SNL model. Pain hypersensitivity was assessed by behavioral analysis. ER stress marker and MANF expression was analyzed in the DRG.
Expression of ER stress marker and MANF was increased in SNL model. ER stress inhibitor piqfithrin reduced pain hypersensitivity and MANF expression after the SNL. Nerve injury induced ER-stress might lead to the development of neuropathic pain via MANF expression.

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] 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] 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] 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] 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
• [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
• [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] Tumor necrosis factor-alpha induces expression of C/EBP-beta in primary afferent neurons following nerve injury. (2014)
  • Author(s): Sasaki M, Hashimoto S, Sawa T, Amaya F
  • Journal Title: Neuroscience Volume: 279 Pages: 1-9
  • DOI: 10.1016/j.neuroscience.2014.08.032
  • Peer Reviewed / Acknowledgement Compliant
• [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] 新規栄養因子MANFの一次知覚神経における発現と 神経障害モデルにおける発現変化 (2015)
  • Author(s): 山口陽輔
  • Organizer: 日本疼痛学会
  • Place of Presentation: 熊本
  • Year and Date: 2015-07-03 – 2015-07-04