Integrative understanding of epigenetic silencing in neuropathic pain

• Project/Area Number: 26830048
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Niigata University
• Principal Investigator: Uchida Hitoshi 新潟大学, 脳研究所, 助教 (30549621)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 神経障害性疼痛 / エピジェネティクス / NRSF / 脊髄後根神経節 / 遺伝子発現 / 転写共役因子

Outline of Final Research Achievements

We have previously provided evidence that epigenetic gene silencing via neuron restrictive silencer factor (NRSF) is important in nerve injury-induced neuropathic pain. The present study revealed that injury induced the expressions of co-factors of NRSF and histone modifying enzymes in the primary afferents. Also, we showed that histone deacetylase inhibitors ameliorated morphine resistance in neuropathic pain via cancellation of the epigenetic silencing of mu opioid receptor gene.

Research Products

• [Journal Article] Histone deacetylase inhibitors relieve morphine resistance in neuropathic pain after peripheral nerve injury (2015)
  • Author(s): Uchida H, Matsushita Y, Araki K, Mukae T,Ueda H
  • Journal Title: J Pharmacol Sci Volume: 128（4） Issue: 4 Pages: 208-211
  • DOI: 10.1016/j.jphs.2015.07.040
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic modification in neuropathic pain (2015)
  • Author(s): Hiroshi Ueda and Hitoshi Uchida
  • Journal Title: Current Pharmaceutical Design Volume: 21 Issue: 7 Pages: 849-867
  • DOI: 10.2174/1381612820666141027113923
  • Peer Reviewed
• [Journal Article] Lysophosphatidic acid and its receptors LPA1 and LPA3 mediate paclitaxel-induced neuropathic pain in mice. (2014)
  • Author(s): Uchida H, Nagai J, Ueda H
  • Journal Title: Mol Pain Volume: 10:71 Pages: 1-7
  • DOI: 10.1186/1744-8069-10-71
  • Peer Reviewed / Open Access
• [Presentation] 神経障害性疼痛誘発因子リゾホスファチジン酸によるミエリン関連遺伝子の転写抑制機構 (2015)
  • Author(s): 内田仁司、植田弘師
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-03-19
• [Presentation] 慢性疼痛とエピジェネティクス (2015)
  • Author(s): 内田仁司、植田弘師
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-03-19
• [Presentation] 断続的冷温負荷による線維筋痛症モデルに対するドネペジルの疼痛改善作用 (2014)
  • Author(s): 内田仁司、迎武紘、植田弘師
  • Organizer: 第67回日本薬理学会西南部会
  • Place of Presentation: 北九州市
  • Year and Date: 2014-11-23
• [Presentation] 創薬に向けた線維筋痛症モデル動物の病態解析と治療戦略 (2014)
  • Author(s): 内田仁司、植田弘師
  • Organizer: 日本線維筋痛症学会第6回学術集会
  • Place of Presentation: 長野市
  • Year and Date: 2014-09-14
• [Presentation] 神経障害性疼痛原因分子LPAによる脱髄とアセチル化修飾 (2014)
  • Author(s): 内田仁司、濱田将徳、植田弘師
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-06-21