Epigenetic regulation underlying development of chronic pain caused by adipokines

• Project/Area Number: 21791469
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Wakayama Medical University
• Principal Investigator: KIGUCHI Norikazu 和歌山県立医科大学, 医学部, 講師 (90433341)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アディポサイトカイン / エピジェネティクス / ケモカイン / レプチン / マクロファージ / サイトカイン / MIP / ヒストン / 神経障害性疼痛 / 好中球 / CXCL2 / CCL3

Research Abstract

Leptin, an adipokine, up-regulated the chemokine macrophage inflammatory proteins(MIPs) in macrophages. The expression of MIPs was increased in the injured peripheral nerves, and the blockade of MIPs signaling prevented nerve injury-induced neuropathic pain and neuroinflammation. Moreover, MIPs expression was enhanced by the overacetylation of histones. In conclusion, adipokines play key roles in the development of neuropathic pain, accompanied by epigenetic augmentation of chemokine expressions in inflammatory cells.

Research Products

• [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, Kobayashi Y, Maeda T, Fukazawa Y, Tohya K, Kimura M, Kishioka S
  • Journal Title: J. Pharmacol. Exp. Ther. Volume: 340(3) Pages: 577-587
  • Peer Reviewed
• [Journal Article] Chemokines and cytokines in neuroinflammation leading to neuropathic pain (2012)
  • Author(s): Kiguchi N, Kobayashi Y, Kishioka S
  • Journal Title: Curr. Opin. Pharmacol Volume: 12(1) Pages: 55-61
• [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] Chemokines and cytokines in neuroinflammation leading to neuropathic pain (2012)
  • Author(s): Kiguchi N, et al
  • Journal Title: Curr Opin Pharmacol Volume: 12(invited) Issue: 1 Pages: 55-61
  • DOI: 10.1016/j.coph.2011.10.007
• [Journal Article] Inhibition of morphine tolerance is mediated by painful stimuli <i>via</i> central mechanisms (2012)
  • Author(s): Iwai S, Kiguchi N, et al
  • Journal Title: Drug Discoveries & Therapeutics Volume: 6 Issue: 1 Pages: 31-37
  • DOI: 10.5582/ddt.2012.v6.1.31
  • NAID: 130005054734
  • ISSN: 1881-7831, 1881-784X
  • Peer Reviewed
• [Journal Article] 神経炎症が関与する末梢神経障害性疼痛のメカニズム (2011)
  • Author(s): 木口倫一、岸岡史郎
  • Journal Title: ペインクリニック Volume: 32(10) Pages: 1499-1509
• [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] Macrophage inflammatory protein-1alpha mediates the development of neuropathic pain following peripheral nerve injury through interleukin-1 beta up-regulation (2010)
  • Author(s): Kiguchi N, Maeda T, Kobayashi Y, Fukazawa Y, Kishioka S
  • Journal Title: Pain Volume: 149(2) Pages: 305-315
  • Peer Reviewed
• [Journal Article] CC-chemokine MIP-1τin the spinal cord contributes to nerve injury-induced neuropathic pain (2010)
  • Author(s): Kiguchi N, Kobayashi Y, Maeda T, Saika F, Kishioka S
  • Journal Title: Neurosci. Lett. Volume: 484(1) Pages: 17-21
  • 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, et al.
  • Journal Title: Pain Volume: 149(2) Pages: 305-315
  • Peer Reviewed
• [Journal Article] CC-chemokine MIP-1α in the spinal cord contributes to nerve injury-induced neuropathic pain (2010)
  • Author(s): Kiguchi N, et al.
  • Journal Title: Neurosci.Lett. Volume: 484 Pages: 17-21
  • 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, et al.
  • Journal Title: Biol.Pharm.Bull. Volume: 33(6) Pages: 1011-1014
  • NAID: 130000247970
  • Peer Reviewed
• [Journal Article] Activation of extracellular signal-regulated kinase in sciatic nerve contributes to neuropathic pain after partial sciatic nerve ligation in mice (2009)
  • Author(s): Kiguchi N, Maeda T, Kobayashi Y, Fukazawa Y, Kishioka S
  • Journal Title: Anesth. Analg. Volume: 109(4) Pages: 1305-1311
  • Peer Reviewed
• [Journal Article] Leptin derived from adipocytes in injured peripheral nerves facilitates development of neuropathic pain via macrophage stimulation (2009)
  • Author(s): Maeda T, Kiguchi N, Kobayashi Y, Ikuta T, Ozaki M, Kishioka S
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 106(31) Pages: 13076-13081
  • Peer Reviewed
• [Journal Article] Leptin enhances CC-chemokine ligand expression in cultured murine macrophage (2009)
  • Author(s): Kiguchi N, Maeda T, Kobayashi Y, Fukazawa Y, Kishioka S
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 384(3) Pages: 311-315
  • Peer Reviewed
• [Journal Article] Leptin derived from adipocytes in injured peripheral nerves facilitates development of neuropathic pain via macrophage stimulation (2009)
  • Author(s): Maeda T, Kiguchi N, et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA 106(31) Pages: 13076-13081
  • Peer Reviewed
• [Journal Article] Leptin enhances CC-chemokine ligand expression in cultured murine macrophage (2009)
  • Author(s): Kiguchi N, et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 384(3) Pages: 311-315
  • Peer Reviewed
• [Journal Article] Activation of extracellular signal-regulated kinase in sciatic nerve contributes to neuropathic pain after partial sciatic nerve ligation in mice (2009)
  • Author(s): Kiguchi N, et al.
  • Journal Title: Anesth.Analg. 109(4) Pages: 1305-1311
  • Peer Reviewed
• [Journal Article] Chapter 14 Involvement of inflammatory mediators in neuropathic pain caused by vincristine (2009)
  • Author(s): Kiguchi N, et al.
  • Journal Title: Int.Rev.Neurobiol. 85 Pages: 179-190
• [Journal Article] Suppressive effect of imipramine on vincristine-induced mechanical allodynia in mice (2009)
  • Author(s): Saika F, Kiguchi N, et al.
  • Journal Title: Biol.Pharm.Bull. 32(7) Pages: 1231-1234
  • NAID: 130000117223
  • Peer Reviewed
• [Presentation] Macrophage inflammatory proteins produce peripheral neuroinflammation leading to neuropathic pain (2012)
  • Author(s): 木口倫一, 小林悠佳, 岸岡史郎
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] The crosstalk between macrophages and T-lymphocytes plays a crucial role in neuropathic pain (2012)
  • Author(s): 小林悠佳、木口倫一, 他
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] MIP-2が担う神経障害性疼痛形成機構における好中球の役割 (2011)
  • Author(s): 木口倫一, 小林悠佳, 岸岡史郎
  • Organizer: 第120回日本薬理学会近畿部会
  • Place of Presentation: 京都
  • Year and Date: 2011-11-11
• [Presentation] Augmentation of MIP-2/CXCR2 axis due to histone H3 acetylation in injured peripheral nerves contributes to neuropathic pain (2011)
  • Author(s): Kiguchi N, Kobayashi Y, Kishioka S
  • Organizer: Italian-Japanese International Seminar for Neurosciences
  • Place of Presentation: Sendai
  • Year and Date: 2011-09-01
• [Presentation] Augmentation of MIP-2/CXCR2 axis due to histone H3 acetylation in injured peripheral nerves contributes to neuropathic pain (2011)
  • Author(s): Kiguchi N, et al
  • Organizer: Italian-Japanese International Seminar for Neurosciences
  • Place of Presentation: 仙台
  • Year and Date: 2011-09-01
• [Presentation] Nicotinic effects and its receptor subtypes-nicotine-induced inhibition of nociceptive pain and neuropathic pain- (2011)
  • Author(s): Kishioka S, Kobayashi Y, Kiguchi N
  • Organizer: Italian-Japanese International Seminar for Neurosciences
  • Place of Presentation: 仙台(招待講演)
  • Year and Date: 2011-09-01
• [Presentation] GITRL-GITR pathway involves in neuropathic pain through the crosstalk between macrophages and T-lymphocytes (2011)
  • Author(s): Kobayashi Y, Kiguchi N, et al
  • Organizer: Italian-Japanese International Seminar for Neurosciences
  • Place of Presentation: 仙台
  • Year and Date: 2011-09-01
• [Presentation] ヒストンアセチル化に基づくCXCL2発現増加は神経障害性疼痛に関与する (2011)
  • Author(s): 木口倫一, 他
  • Organizer: 第79回和歌山医学会総会
  • Place of Presentation: 和歌山
  • Year and Date: 2011-07-10
• [Presentation] MIP-1βは神経障害性疼痛を惹起する (2011)
  • Author(s): 雑賀史浩、木口倫一, 他
  • Organizer: 第79回和歌山医学会総会
  • Place of Presentation: 和歌山
  • Year and Date: 2011-07-10
• [Presentation] Up-regulation of MIP-2 and its receptor through histone acetylation involves in nerve injury-induced neuropathic pain (2011)
  • Author(s): 木口倫一, 他
  • Organizer: 第84回日本薬理学会
  • Place of Presentation: (誌上開催)
  • Year and Date: 2011-03-22
• [Presentation] Up-regulation of MIP-2 and its receptor through histone acetylation involves in nerve injury-induced neuropathic pain (2011)
  • Author(s): 木口倫一, 前田武彦, 小林悠佳, 岸岡史郎
  • Organizer: 第84回日本薬理学会年会
• [Presentation] 坐骨神経傷害後のアロディニア形成に及ぼすMIP-1βの影響 (2010)
  • Author(s): 雑賀史浩、木口倫一, 他
  • Organizer: 第118回日本薬理学会近畿部会
  • Place of Presentation: 大阪
  • Year and Date: 2010-11-19
• [Presentation] Macrophage inflammatory protein-1α mediates the pathgenesis of neuropathic pain (2010)
  • Author(s): Kiguchi N, et al.
  • Organizer: Neuroscience2010
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-14
• [Presentation] Macrophage inflammatory protein-1τmediates the pathogenesis of neuropathic pain (2010)
  • Author(s): Kiguchi N, Maeda T, Kobayashi Y, Fukazawa Y, Kishioka S
  • Organizer: Neuroscience 2010 SfN's 40^<th> annual meeting
  • Place of Presentation: San Diego, CA
  • Year and Date: 2010-11-04
• [Presentation] Role of macrophage inflammatory protein-1 in the pathogenesis of neuropathic pain (2010)
  • Author(s): Kiguchi N, Maeda T, Kobayashi Y, Kishioka S
  • Organizer: Molecular Targets for Novel Pain Therapeutics
  • Place of Presentation: Parghelia(VV), Calabria, Italy
  • Year and Date: 2010-09-24
• [Presentation] Role of macrophage inflammatory protein-1 in the pathogenesis of neuropathic pain (2010)
  • Author(s): Kiguchi N, et al.
  • Organizer: Molecular Targets for Novel Pain Therapeutics From basic research to clinical translation
  • Place of Presentation: Calabria, Italy
  • Year and Date: 2010-09-24
• [Presentation] Functional role of spinal ceramide in the development of neuropathic pain (2010)
  • Author(s): Kobayashi Y, Kiguchi N, et al.
  • Organizer: Molecular Targets for Novel Pain Therapeutics From basic research to clinical translation
  • Place of Presentation: Calabria, Italy
  • Year and Date: 2010-09-23
• [Presentation] Macrophage inflammatory protein-1 alpha plays a key role in the development of neuropathic pain. New Perspectives in Neuroscience (2010)
  • Author(s): Kiguchi N, Maeda T, Kobayashi Y, Saika F, Kishioka S
  • Organizer: Joint Meeting of Young Italian and Japanese Neuroscientists
  • Place of Presentation: Naples, Italy
  • Year and Date: 2010-09-21
• [Presentation] Macrophage inflammatory protein-1α plays a key role in the development of neuropathic pain (2010)
  • Author(s): Kiguchi N, et al.
  • Organizer: New Perspectives in Neuroscience : Joint Meeting of Young Italian and Japanese Neuroscientists
  • Place of Presentation: Naples, Italy
  • Year and Date: 2010-09-21
• [Presentation] Spinal ceramide contributes to nerve injury-induced neuropathic pain (2010)
  • Author(s): Kobayashi Y, Kiguchi N, et al.
  • Organizer: New Perspectives in Neuroscience : Joint Meeting of Young Italian and Japanese Neuroscientists
  • Place of Presentation: Naples, Italy
  • Year and Date: 2010-09-21
• [Presentation] Spinal ceramide is responsible for the development of neuropathic pain (2010)
  • Author(s): 小林悠佳、木口倫一, 他
  • Organizer: Neuro2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-04
• [Presentation] Macrophage inflammatory protein-1τmediates the development of neuropathic pain following peripheral nerve injury (2010)
  • Author(s): 木口倫一, 前田武彦, 小林悠佳, 深澤洋滋, 岸岡史郎
  • Organizer: Neuro2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] Macropharge inflammatory protein-1α mediates the development of neuropathic pain following peripheral nerve injury (2010)
  • Author(s): 木口倫一, 他
  • Organizer: Neuro2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [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, 小林悠佳, 岸岡史郎
  • 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
  • Year and Date: 2010-08-27
• [Presentation] 神経障害性疼痛におけるHMGB1の関与 (2010)
  • Author(s): 前田武彦、木口倫一, 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
  • Year and Date: 2010-08-27
• [Presentation] Leptin enhances IL-1υand MIP-1τハexpression in murine macrophages (2010)
  • Author(s): 木口倫一, 前田武彦, 小林悠佳, 岸岡史郎
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] レプチンはマクロファージにおけるIL-1βおよびMIP-1αの発現を増加させる (2010)
  • Author(s): 木口倫一, 他
  • Organizer: 第83回日本薬理学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] HMGB1によるレプチンシグナル活性化は神経障害性疼痛の形成に関与する (2010)
  • Author(s): 前田武彦、木口倫一, 他
  • Organizer: 第83回日本薬理学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] セラミドは脊髄におけるミクログリアの活性化および炎症性サイトカインの遊離を介して神経障害性疼痛を調節する (2010)
  • Author(s): 小林悠佳、木口倫一, 他
  • Organizer: 第83回日本薬理学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] 炎症性疼痛下におけるモルヒネ耐性および身体的依存形成 (2009)
  • Author(s): 木口倫一、岸岡史郎
  • Organizer: 第37回和歌山悪性腫瘍研究会
  • Place of Presentation: 和歌山
  • Year and Date: 2009-12-05
• [Presentation] 神経障害性疼痛におけるセラミドの関与 (2009)
  • Author(s): 小林悠佳、木口倫一, 他
  • Organizer: 第116回日本薬理学会近畿部会
  • Place of Presentation: 大津
  • Year and Date: 2009-11-13
• [Presentation] シュワン細胞におけるERKの活性は坐骨神経結紮による神経障害性疼痛に関与する (2009)
  • Author(s): 木口倫一, 他
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-18
• [Presentation] CCケモカインMIP-1αは末梢神経傷害後のアロディニア形成を促進する (2009)
  • Author(s): 木口倫一, 前田武彦, 小林悠佳, 岸岡史郎
  • Organizer: 第30回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-08-28
• [Presentation] CCケモカインMIP-1βは末梢神経傷害後のアロディニア形成を促進する (2009)
  • Author(s): 木口倫一, 他
  • Organizer: 第30回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-08-28
• [Presentation] MIP-1αの介在する神経障害性疼痛形成機構におけるマクロファージの役割 (2009)
  • Author(s): 木口倫一, 前田武彦, 小林悠佳, 岸岡史郎
  • Organizer: 第115回日本薬理学会近畿部会
  • Place of Presentation: 金沢
  • Year and Date: 2009-06-26
• [Book] Involvement of inflammatory mediators in neuropathic pain caused by vincristine (2009)
  • Author(s): Kiguchi N, Maeda T, Kobayashi Y, Saika F, Kishioka S
  • Publisher: Int. Rev. Neurobiol.
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/dept/igakubu/160416/index.html
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/dept/igakubu/160416/index.html
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/dept/igakubu/160416/index.html
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/dept/igakubu/160416/index.html