Pharmacologic plasticity of analgesic drugs in neuropathic pain states-measurement with monoamines in the spinal cord-

• Project/Area Number: 20591823
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Gunma University
• Principal Investigator: OBATA Hideaki Gunma University, 医学部, 講師 (20302482)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ノルアドレナリン / セロトニン / マイクロダイアライシス / 神経障害性疼痛 / 脊髄 / ラット / ノルアドレナリソ

Research Abstract

We examined mechanisms of antinociceptive effects of drugs such as antidepressant and gabapentin for neuropathic pain using rat pain models. We also measured spinal noradrenalin and serotonin level after the drug injection using microdialysis. We demonstrated that these drugs increased noradrenalin level in the spinal cord and the noradrenalin increase strongly contributed to the inhibitory effect for neuropathic pain.

Research Products

• [Journal Article] Nontoxic genetic engineering of mesenchymal stem cells using serum-compatible pullulan-spermine/DNA anioplexes. (2011)
  • Author(s): Thakor D, Teng YD, Obata H, Nagane K, Saito S, Tabata Y
  • Journal Title: Tissue Eng Part C Methods. 17 Pages: 131-44
  • Peer Reviewed
• [Journal Article] Nontoxic genetic engineering of mesenchymal stem cells using serum-compatible nullulan-snermine/DNA anionlexes. (2011)
  • Author(s): Thakor D
  • Journal Title: Tissue Eng Part C Methods Volume: 17 Pages: 131-144
  • Peer Reviewed
• [Journal Article] Long-term effect of sciatic nerve block with slow-release lidocaine in a rat model of postoperative pain. (2010)
  • Author(s): Tobe M, Obata H, Suto T, Yokoo H, Nakazato Y, Tabata Y, Saito S.
  • Journal Title: Anesthesiology. 112 Pages: 1473-81
  • Peer Reviewed
• [Journal Article] Lack of analgesic efficacy of spinal ondansetron on thermal and mechanical hypersensitivity following spinal nerve ligation in the rat. (2010)
  • Author(s): Peters CM, Hayashida K, Ewan EE, Nakajima K, Obata H, Xu Q, Yaksh TL, Eisenach JC.
  • Journal Title: Brain Res. 1352 Pages: 83-93
  • Peer Reviewed
• [Journal Article] Activation of astrocytes in the spinal cord contributes to the development of bilateral allodynia after peripheral nerve injury in rats. (2010)
  • Author(s): Obata H, Sakurazawa S, Kimura M, Saito S.
  • Journal Title: Brain Res. 1363 Pages: 72-80
  • Peer Reviewed
• [Journal Article] Monoamine-dependent, opioid-independent antihypersensitivity effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a postoperative pain model in rats. (2010)
  • Author(s): Obata H, Kimura M, Nakajima K, Tobe M, Nishikawa K, Saito S.
  • Journal Title: J Pharmacol Exp Ther. 334 Pages: 1059-65
  • Peer Reviewed
• [Journal Article] 慢性痛の分子化学的機序と臨床薬理学 (2010)
  • Author(s): 小幡英章,荻野祐一
  • Journal Title: 麻酔 59
• [Journal Article] Technical communication : percutaneous radiofrequency mandibular nerve rhizotomy guided by high-speed real-time computed tomography fluoroscopy. (2010)
  • Author(s): Koizuka S, Saito S, Tobe M, Sekimoto K, Obata H, Koyama Y.
  • Journal Title: Anesth Analg. 111 Pages: 763-7
  • Peer Reviewed
• [Journal Article] Monoamine-dependent, opioid-independent antihypersensitivity effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a postonerative pain model in rats. (2010)
  • Author(s): Obata H
  • Journal Title: J Pharmacol Exp Ther Volume: 334 Pages: 1059-1065
  • Peer Reviewed
• [Journal Article] Long-term effect of sciatic nerve block with slow-release lidocaine in a rat model of postoperative pain. (2010)
  • Author(s): Tobe M
  • Journal Title: Anesthesiology Volume: 112 Pages: 1473-1481
  • Peer Reviewed
• [Journal Article] Activation of astrocytes in the spinal cord contributes to the development of bilateral allodynia after peripheral nerve injury in rats. (2010)
  • Author(s): Obata H
  • Journal Title: Brain Res Volume: 1363 Pages: 72-80
  • Peer Reviewed
• [Journal Article] Lack of analgesic efficacy of spinal ondansetron on thermal and mechanical hype rsensitivity following spinal nerve ligation in the rat. (2010)
  • Author(s): Peters CM
  • Journal Title: Brain Res Volume: 1352 Pages: 83-93
  • Peer Reviewed
• [Journal Article] 慢性痛の分子化学的機序と臨床薬理学 (2010)
  • Author(s): 小幡英章
  • Journal Title: 麻酔 Volume: 59
• [Journal Article] The nociceptive mechanism of 5-hydroxytryptamine released into the peripheral tissue in acute paininflammatory in rats. (2009)
  • Author(s): Nakajima K, Obata H, Ito N, Goto F, Saito S.
  • Journal Title: Eur J Pain. 13 Pages: 441-7
  • Peer Reviewed
• [Journal Article] Percutaneous radio-frequency thermocoagulation of the Gasserian ganglion guided by high-speed real-time CT fluoroscopy. (2009)
  • Author(s): Koizuka S, Saito S, Sekimoto K, Tobe M, Obata H, Koyama Y.
  • Journal Title: Neuroradiology 51 Pages: 563-6
  • Peer Reviewed
• [Journal Article] Spinal microglial expression and mechanical hypersensitivity in a postoperative pain model : comparison with a neuropathic pain model. (2009)
  • Author(s): Ito N, Obata H, Saito S.
  • Journal Title: Anesthesiology. 111 Pages: 640-8
  • Peer Reviewed
• [Journal Article] α2受容体をターゲットにした慢性疼痛の治療 (2009)
  • Author(s): 小幡英章,林田健一郎,中島邦枝,齋藤繁
  • Journal Title: ペインクリニック 30
• [Journal Article] CRPSの薬物療法:ガバペンチンと抗うつ薬 (2009)
  • Author(s): 小幡英章,林田健一郎
  • Journal Title: ペインクリニック 30
• [Journal Article] Spinal microglial expression and mechanical hypersensitivity in a postoperative pain model : comparison with a neuropathic pain model. (2009)
  • Author(s): Ito N
  • Journal Title: Anesthesiology 113 Pages: 640-8
  • Peer Reviewed
• [Journal Article] The nociceptive mechanism of 5-hydroxytryptamine released into the peripheral tissue in acute inflammatory pain in rats (2009)
  • Author(s): Nakajima K
  • Journal Title: Eur J Pain 13 Pages: 441-7
  • Peer Reviewed
• [Journal Article] Percutaneous radio-frequency thermocoagulation of the Gasserian ganglion guided by high-speed real-time CT fluoroscopy (2009)
  • Author(s): Koizuka S
  • Journal Title: Neuroradiology 51 Pages: 563-6
  • Peer Reviewed
• [Journal Article] 先取り鎮痛法 (2009)
  • Author(s): 小幡英章
  • Journal Title: 整形・災害外科 52 Pages: 563-569
• [Journal Article] α2受容体をターゲットにした慢性疼痛の治療 (2009)
  • Author(s): 小幡英章
  • Journal Title: ペインクリニック 30
• [Journal Article] CRPSの薬物療法:ガバペンチンと抗うつ薬 (2009)
  • Author(s): 小幡英章
  • Journal Title: ペインクリニック 30
• [Journal Article] 末梢の急性炎症に対する5-HTの作用機序 (2009)
  • Author(s): 小幡英章
  • Journal Title: 生体の科学 60 Pages: 346-347
• [Journal Article] Gabapentin acts within the locus coeruleus to alleviate neuropathic pain. (2008)
  • Author(s): Hayashida K, Obata H, Nakajima K, Eisenach JC.
  • Journal Title: Anesthesiology. 109 Pages: 1077-84
  • Peer Reviewed
• [Journal Article] α2受容体をターゲットにした慢性疼痛の治療 (2008)
  • Author(s): 小幡英章,林田健一郎,中島邦枝,齋藤繁
  • Journal Title: ペインクリニック 29 Pages: 239-249
• [Journal Article] 疼痛治療に用いる薬物-Updata-:抗うつ薬(TCA, SNRI, SSRI) (2008)
  • Author(s): 小幡英章
  • Journal Title: ペインクリニック 29 Pages: 625-632
• [Journal Article] CRPSの薬物療法:ガバペンチンと抗うつ薬 (2008)
  • Author(s): 小幡英章,林田健一郎
  • Journal Title: ペインクリニック 29 Pages: 1189-1197
• [Journal Article] 慢性疼痛におけるセロトニンの役割 (2008)
  • Author(s): 小幡英章
  • Journal Title: 麻酔 57
• [Journal Article] Gabapentin acts within the locus coeruleus to alleviate neuropathic pain (2008)
  • Author(s): Hayashida K, Obata H, et al.
  • Journal Title: Anesthesiology 109 Pages: 1077-1084
  • Peer Reviewed
• [Journal Article] A novel bFGF-GH injection therapy for two patients with severe ischemic limb pain (2008)
  • Author(s): Ito N, Saito S, Yamada MH, Koizuka S, Obata H, et al.
  • Journal Title: Journal of Anesthesia 22 Pages: 449-452
  • Peer Reviewed
• [Journal Article] The nociceptive mechanism of 5-hydroxytryptamine released into the nerinheral tissue in acute inflammatory nain in rats
  • Author(s): Nakajima K, Obata H, et al.
  • Journal Title: European Journal of Pain (in press)
  • Peer Reviewed
• [Presentation] Antihypersensitivity effects of tramadol hydrochloride in a rat model of postoperative pain. (2010)
  • Author(s): Kimura M, Obata H, Saito S.
  • Organizer: Society for Neuroscience Annual Meeting 2010
  • Place of Presentation: SanDiego Convention Center, San Diego, USA
  • Year and Date: 2010-11-14
• [Presentation] Antihypersensitivity effects of tramadol hydrochloride in a rat model of postoperative pain (2010)
  • Author(s): Kimura M
  • Organizer: Society for Neuroscience Annual Meeting 2010
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-14
• [Presentation] Spinal microglial expression and mechanical hypersensitivity in a postoperative pain model -comparison with a neuropathic pain model-. (2010)
  • Author(s): Obata H, Ito N, Saito S.
  • Organizer: 13th world congress on pain
  • Place of Presentation: Montreal Convention Centre, Montreal, Canada
  • Year and Date: 2010-08-31
• [Presentation] Long-term effect of slow releasing lidocaine sheet and particle in a rat model of postoperative pain. (2010)
  • Author(s): Suto T, Tobe H, Obata H, Saito S, Goto F.
  • Organizer: 13th world congress on pain
  • Place of Presentation: Montreal Convention Centre, Montreal,Canada
  • Year and Date: 2010-08-31
• [Presentation] 塩酸トラマドールの鎮痛作用機序 -ラット術後痛モデルとマイクロダイアリシスでの検討- (2010)
  • Author(s): 木村雅文
  • Organizer: 第32回日本疼痛学会
  • Place of Presentation: 京都市
  • Year and Date: 2010-07-03
• [Presentation] ミルナシプランおよびパロキセチンの鎮痛メカニズム (2010)
  • Author(s): 中島邦枝
  • Organizer: 日本麻酔科学会第57回学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2010-06-04
• [Presentation] A long-term effect of sciatic nerve block with slow releasing lidocaine in a rat model of postoperative pain. (2009)
  • Author(s): Tobe M
  • Organizer: Society for Neuroscience Annual Meeting 2009
  • Place of Presentation: Chicago
  • Year and Date: 2009-10-20
• [Presentation] Spinal microglial expression and mechanical hypersensitivity in a postoperative pain model. (2009)
  • Author(s): Obata H, Ito N, Saito S.
  • Organizer: Society for Neuroscience Annual Meeting 2009
  • Place of Presentation: Tinley Park-Convention Center, Chicago, USA
  • Year and Date: 2009-10-18
• [Presentation] Spinal microglial expression and mechanical hypersensitivity in a postoperative pain model. (2009)
  • Author(s): 小幡英章
  • Organizer: Society for Neuroscience Annual Meeting 2009
  • Place of Presentation: Chicago, U.S.A.
  • Year and Date: 2009-10-18
• [Presentation] 抗うつ薬(SNRI/SSRI)の鎮痛作用、鎮痛補助薬-使用におけるエビデンスの確立に向けて (2009)
  • Author(s): 小幡英章
  • Organizer: 第3回日本緩和医療薬学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-17
• [Presentation] ガバペンチンは下行性ノルアドレナリン作動性神経を活性化して神経障害性疼痛を抑制する (2009)
  • Author(s): 小幡英章、林田健一郎、中島邦枝、齋藤繁、Eisenach JC
  • Organizer: 日本麻酔科学会第56回学術集会
  • Place of Presentation: ポートピアホテル、神戸市
  • Year and Date: 2009-08-16
• [Presentation] Antinociceptive mechanism of serotonin noradrenaline reuptake inhibitor (SNRI) in a rat model of neuropathic pain. (2008)
  • Author(s): Nakajima K, Obata H, Ito N, Saito S.
  • Organizer: Society for Neuroscience Annual Meeting 2008
  • Place of Presentation: Washington DC Convention Center, Washington DC, USA
  • Year and Date: 2008-11-17
• [Presentation] Antinociceptive effects of SNRI mainly depends on noradrenergic mechanisms in a rat model of neuronathic pain (2008)
  • Author(s): Nakajima K, Obata H, Saito S.
  • Organizer: Society for Neuroscience Annual Meeting 2008
  • Place of Presentation: Washington DC
  • Year and Date: 2008-11-15
• [Presentation] Serotonin and noradrenaline reuptake inhibition by milnacipran reduces mechanical hypersensitivity after paw incision in rats. (2008)
  • Author(s): Obata H, Nakajima K, Saito S, Goto F.
  • Organizer: 12th world congress on pain
  • Place of Presentation: Convention Center, Glasgow, UK
  • Year and Date: 2008-10-03
• [Presentation] Serotonin noradrenaline reuptake inhibitor(SNRI)の鎮痛メカニズム (2008)
  • Author(s): 中島邦枝、小幡英章、斎藤繁
  • Organizer: 日本ペインクリニック学会第42回大会
  • Place of Presentation: 福岡国際会議場、福岡市
  • Year and Date: 2008-07-20
• [Presentation] SNRI(ミルナシプラン)の鎮痛作用-ラット術後痛モデルでの検討- (2008)
  • Author(s): 小幡英章、中島邦枝、伊藤奈穂美、斎藤繁
  • Organizer: 日本麻酔科学会第55回学術集会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2008-06-14
• [Presentation] マイクロダイアリシス法を用いた脊髄後角におけるNA・5-HT の同時測定 (2008)
  • Author(s): 中島邦枝、小幡英章、斎藤繁
  • Organizer: 日本麻酔科学会第55回学術集会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2008-06-13