Study on pathophysiological mechanism underlying leptin-induced exacerbation of neuropathic pain

• Project/Area Number: 22590090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Nigata University of Phermacy and Applied Life Sciences
• Principal Investigator: OZAKI Masanobu 新潟薬科大学, 薬学部, 教授 (30094650)
• Co-Investigator(Kenkyū-buntansha): MAEDA Takehiko 新潟薬科大学, 薬学部, 教授 (50271010) ; KISHIOKA Shiroh 和歌山県立医科大学, 医学部, 教授 (60137255)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 疼痛 / クロマチン免疫沈降 / ヌクレオカイン / 神経障害性疼痛 / HMGB1

Research Abstract

We studied the mechanism underlying leptin release from adipocytes, which is a mediator for the induction of neuropathic pain underlying of neuropathic pain. The present results indicated that HMGB1, high mobility group box 1 was released from injured peripheral nerve tissue and then, acted on adipocytes to promote leptin release. It was elucidated that HMGB1 was an immediate early mediator for induction of neuropathic pain.

Research Products

• [Journal Article] The critical role of spinal ceramide in the development of partial sciatic nerve ligation-induced neuropathic pain in mice (2012)
  • Author(s): Kobayashi Y, Kiguchi N, Maeda T, Ozaki M, Kishioka S.
  • Journal Title: Biochem Biophys Res Commun Volume: 421 Issue: 2 Pages: 318-322
  • DOI: 10.1016/j.bbrc.2012.03.153
  • Peer Reviewed
• [Journal Article] Epigenetic augmentation of the macrophage inflammatory protein 2/C-X-C chemokine receptor type 2 axis through histone H3 acetylation in injured peripheral nerves elicits neuropathic pain (2012)
  • Author(s): Kiguchi N, et al
  • Journal Title: J Pharmacol Exp Ther Volume: 340 Issue: 3 Pages: 577-587
  • DOI: 10.1124/jpet.111.187724
  • Peer Reviewed
• [Journal Article] Availability of serum corticosterone level for quantitative evaluation of morphine withdrawal in mice (2011)
  • Author(s): Ueno K, Maeda T, Kiguchi N, Kobayashi Y, Ozaki M, Kishioka S.
  • Journal Title: Drug Discov Ther Volume: 5 Pages: 71-75
  • NAID: 130005054697
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22466143
  • Peer Reviewed
• [Journal Article] Pharmacological relationship between nicotinic and opioid systems in analgesia and corticosterone elevation (2011)
  • Author(s): Yamamoto A
  • Journal Title: Life Sci Volume: 89 Issue: 25-26 Pages: 956-961
  • DOI: 10.1016/j.lfs.2011.10.004
  • Peer Reviewed
• [Journal Article] Increment of activated serine/threonine protein phosphatase in brain membrane fraction synchronized with antinociceptive effect of morphine in mice (2010)
  • Author(s): Maeda T, Kiguchi N, Kobayashi Y, Ozaki M, Kishioka S
  • Journal Title: Biol.Pharm. Bull. Volume: 33 Pages: 1011-1014
  • NAID: 130000247970
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20522968
  • Peer Reviewed
• [Journal Article] Macrophage inflammatory protein-1α mediates the development of neuropathic pain following peripheral nerve injury through interleukin-1β up-regulation (2010)
  • Author(s): Kiguchi N, Maeda T, et al.
  • Journal Title: Pain Volume: 149(2) Pages: 305-315
  • Peer Reviewed
• [Journal Article] Increment of activated serine/threonine protein phosphatase in brain membrane fraction synchronized with antinociceptive effect of morphine in mice (2010)
  • Author(s): Maeda T, et al.
  • Journal Title: Biol.Pharm.Bull. Volume: 33(6) Pages: 1011-1014
  • NAID: 130000247970
  • Peer Reviewed
• [Journal Article] CC-chemokine MIP-1α in the spinal cord contributes to nerve injury-induced neuropathic pain (2010)
  • Author(s): Kiguchi N, Kobayashi Y, Maeda T, et al.
  • Journal Title: Neurosci.Lett. Volume: 484 Pages: 17-21
  • Peer Reviewed
• [Journal Article] レプチンと神経障害性疼痛 (2010)
  • Author(s): 前田武彦
  • Journal Title: 医学のあゆみ Volume: 233(7) Pages: 565-565
• [Presentation] 慢性および難治性疼痛発症機序の解明と創薬に向けて (2013)
  • Author(s): 前田武彦,尾崎昌宣
  • Organizer: 日本薬学会第133年会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] TRPチャネルを標的とする新規鎮痛機序の解析 (2013)
  • Author(s): 前田武彦
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 慢性疼痛における脂肪細胞の機能的役割とその制御 (2011)
  • Author(s): 前田武彦
  • Organizer: 第61回日本薬学会近畿支部総会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2011-10-22
• [Presentation] 緩和医療における臨床研究・基礎研究とは (2011)
  • Author(s): 前田武彦
  • Organizer: 第61回日本薬学会近畿支部総会・大会
  • Place of Presentation: 神戸
  • Year and Date: 2011-10-22
• [Presentation] Effect of capsaicin on neuropathic pain through the modulation of interaction of adipocytes and macrophages (2011)
  • Author(s): 前田武彦, 他
  • Organizer: 第84回日本薬理学会
  • Place of Presentation: (誌上開催)
• [Presentation] 神経障害性疼痛におけるマクロファージ活性化および脂肪細胞肥大化に及ぼすカプサイシンの影響 (2010)
  • Author(s): 前田武彦, 他
  • Organizer: 第117回日本薬理学会近畿部会
  • Place of Presentation: 徳島
• [Presentation] レプチンの神経障害性疼痛における役割 (2010)
  • Author(s): 前田武彦, 他
  • Organizer: 第15回アディポサイエンス研究会シンポジウム
  • Place of Presentation: 大阪
• [Presentation] 神経障害性疼痛におけるHMGB1の関与 (2010)
  • Author(s): 前田武彦, 他
  • Organizer: 第31回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 名古屋
• [Presentation] 神経障害性疼痛形成におけるMIP-2の役割 (2010)
  • Author(s): 木口倫一、前田武彦, 他
  • Organizer: 第31回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 名古屋
• [Presentation] Macropharge inflammatory protein 1α mediates the development of neuropathic pain following peripheral nerve injury (2010)
  • Author(s): 木口倫一、前田武彦, 他
  • Organizer: Neuro2010
  • Place of Presentation: 神戸
• [Presentation] Macrophage inflammatory protein-1α plays a key role in the development of neuropathic pain (2010)
  • Author(s): Kiguchi N, Maeda T, et al.
  • Organizer: New Perspectives in Neuroscience : Joint Meeting of Young Italian and Japanese Neuroscientists
  • Place of Presentation: Naples, Italy
• [Presentation] Leptin and neuropathic pain (2010)
  • Author(s): Kishioka S, Maeda T
  • Organizer: Molecular Targets for Novel Pain Therapeutics From basic research to clinical translation
  • Place of Presentation: Calabria, Italy
• [Presentation] Role of macrophage inflammatory protein-1 in the pathogenesis of neuropathic pain (2010)
  • Author(s): Kiguchi N, Maeda T, et al.
  • Organizer: Molecular Targets for Novel Pain Therapeutics From basic research to clinical translation
  • Place of Presentation: Calabria, Italy
• [Presentation] Macrophage inflammatory protein-1α mediates the pathgenesis of neuropathic pain (2010)
  • Author(s): Kiguchi N, Maeda T, et al.
  • Organizer: Neuroscience2010
  • Place of Presentation: San Diego, USA
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/dept/igakubu/160416/index.html