Development of analgesic method by inhibition of synthesis of brain-derived neurotrophic factor (BDNF) exon released from microglia

• Project/Area Number: 19591794
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Okayama University
• Principal Investigator: YOKOYAMA Masataka Okayama University, 大学院・医歯薬学総合研究科, 准教授 (20158380)
• Co-Investigator(Kenkyū-buntansha): ITANO Yoshitarou 岡山大学, 大学院・医歯薬学総合研究科, 助教 (30127542)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経因性疼痛 / 脳由来神経栄養因子 / ミクログリア / エクソン / siRNA / 難治性疼痛 / 遺伝子治療 / ノックダウン

Research Abstract

本研究の主眼は神経因性疼痛におけるミクログリアより放出される脳由来神経栄養因子(BDNF)のエクソンに注目し、BDNFの中でも特異的なエクソン合成抑制による疼痛治療の基礎を確立することを目指した。疼痛モデルで特異的に過剰発現するのはエクソンー1であることを特定した。疼痛モデルにおいて脊髄内にエクソンー1に対するsiRNAを投与し、ミクログリアとニューロンにおけるBDNF合成阻害を観察し、鎮痛効果を検討した。しかし、鎮痛効果は有意ではなく、次の段階としてDNAデコイを作成することとした。

Research Products

• [Journal Article] Expression changes of multiple brain-derived neurotrophic factor transcripts in selective spinal nerve ligation model and complete Freund's adjuvant model (2008)
  • Author(s): Kobayashi H, Yokoyama M, Matsuoka Y, Omori M, Itano Y, Kaku R, Kiyoshi M, Ichikawa H
  • Journal Title: Brain Res 1206 Pages: 13-9
  • Peer Reviewed
• [Journal Article] Effects of selective spinal nerve ligation on acetic acid-induced nociceptive responses and ASIC3 immunoreactivity in the rat dorsal root ganglion (2008)
  • Author(s): Omori M, Yokoyama M, Matsuoka Y, Kobayashi H, Mizobuchi S, Itano Y, Morita K, Ichikawa H
  • Journal Title: Brain Res 1219 Pages: 26-31
  • Peer Reviewed
• [Journal Article] 高用量フェンタニルパッチによる癌性疼痛の1症例 (2008)
  • Author(s): 松崎孝、西江宏行、森松博史、石川慎一、佐藤健治、溝渕知司、中塚秀輝、松三昌樹、横山正尚、森田潔
  • Journal Title: 日本ペインクリニック学会誌 15 Pages: 150-152
  • Peer Reviewed
• [Journal Article] 硬膜外血腫 (2008)
  • Author(s): 横山正尚
  • Journal Title: 日本臨床麻酔学会誌 8 Pages: 134-142
  • NAID: 10020169193
  • Peer Reviewed
• [Journal Article] 硬膜外麻酔 適応と禁忌 (2008)
  • Author(s): 横山正尚
  • Journal Title: 日本臨床麻酔学会誌
  • NAID: 10024949350
  • Peer Reviewed
• [Journal Article] Expression changes of multiple brain-derived neurotrophic factor transcripts in selective spinal nerve ligation model and complete Freund's adjuvant model (2008)
  • Author(s): Kobayashi H, Yokoyama M, et al
  • Journal Title: Brain Res 1206 Pages: 13-19
  • Peer Reviewed
• [Journal Article] Effects of selective spinal nerve ligation on acetic acid-induced nociceptive responses and ASIC3 immunoreactivity in the rat dorsal root ganglion (2008)
  • Author(s): Omori M, Yokoyama M
  • Journal Title: Brain Res 1219 Pages: 26-31
  • Peer Reviewed
• [Journal Article] 高用量フェンタニルパツチによる癌性疼痛の1症例 (2008)
  • Author(s): 松崎孝, 横山正尚, 他
  • Journal Title: 日本ペインクリニック学会誌 15 Pages: 150-152
  • Peer Reviewed
• [Journal Article] 硬膜外血腫 (2008)
  • Author(s): 横山正尚
  • Journal Title: 日本臨床麻酔学会誌 28 Pages: 134-142
  • NAID: 10020169193
  • Peer Reviewed
• [Journal Article] 硬膜外麻酔 適応と禁忌 (2008)
  • Author(s): 横山正尚
  • Journal Title: 日本臨床麻酔学会誌 (in press)
  • NAID: 10024949350
  • Peer Reviewed
• [Journal Article] Altered response to formalin by L5 spinal nerve ligation in rats: a behavioral and molecular study (2007)
  • Author(s): Kaku R, Yokoyama M, et. al.
  • Journal Title: Anesth Analg 104 Pages: 936-943
  • Peer Reviewed
• [Journal Article] Epidural blood patch therapy for chronic whiplash-associated disorder (2007)
  • Author(s): Ishikawa I, Yokoyama M, et. al.
  • Journal Title: Anesth Analg 105 Pages: 809-814
  • Peer Reviewed
• [Journal Article] Expression profiles of BDNF splice variants in cultured DRG neurons stimulated with NGF (2007)
  • Author(s): Matsuoka Y, Yokoyama M
  • Journal Title: Biochemical Biophys Res Commun 362 Pages: 682-688
  • Peer Reviewed
• [Journal Article] 腰椎転移による癌性疼痛にモルヒネ徐放剤から一部フェンタニルパッチ変更が奏効した1症例 (2007)
  • Author(s): 松崎孝、横山正尚、他
  • Journal Title: 日本ペインクリニック学会誌 14 Pages: 140-143
  • Peer Reviewed
• [Journal Article] 免疫抑制剤投与中にみられた下肢難治性疼痛の1症例 (2007)
  • Author(s): 松崎孝、横山正尚、他
  • Journal Title: ペインクリニック 28 Pages: 723-726
  • Peer Reviewed
• [Presentation] IV PCA・持続注入法による術後鎮痛 : モルヒネIV PCA (2008)
  • Author(s): 横山正尚、中塚秀輝、佐藤健治、西江宏行
  • Organizer: 第28回日本臨床麻酔学会
  • Place of Presentation: 京都
• [Presentation] Effects of Selective Spinal Nerve Ligation on Acetic Acid-induced Nociceptive Responses (2008)
  • Author(s): Yokoyama M, Omori M, Matsuoka K, Itano Y, Morita K
  • Organizer: American Society of Anesthesiologists
  • Place of Presentation: Orlando
• [Presentation] Effects of NGF on Expression of ASIC3 and TRPV1 in Cultured Rat DRG Neurons (2008)
  • Author(s): Matsuoka K, Omori M, Itano Y, Yokoyama M, Morita K
  • Organizer: American Society of Anesthesiologists
  • Place of Presentation: Orlando
• [Presentation] Expression of ASIC3 and TRPV1 in cultured rat DRG nervous stimulated with NGF (2008)
  • Author(s): Matsuoka K, Omori M, Itano Y, Yokoyama M
  • Organizer: 12^<th> World Congress on Pain
  • Place of Presentation: Glasgow
• [Presentation] Effects OF selective spinal nerve ligation on acetic acid-induced nociceptive responces and ASIC3 immunoreactivity in the rat dorsal root ganglion (2008)
  • Author(s): Yokoyama M, Omori M, Matsuoka K, Itano Y
  • Organizer: 12^<th> World Congress on Pain
  • Place of Presentation: Glasgow
• [Presentation] Incidence of traumatic cerebrospinal fluid leak following whiplash associated disorders (2008)
  • Author(s): Ishikawa S, Tomotsuka N, Mizobuchi S, Sato K,Moriyama E, Yokoyama M, Morita K
  • Organizer: 12^<th> World Congress on Pain
  • Place of Presentation: Glasgow
• [Presentation] 脊髄神経傑作が酢酸刺激による疼痛行動に及ぼす変化に関する研究 (2008)
  • Author(s): 大森恵、小林浩之、松岡義和、板野義太郎、横山正尚
  • Organizer: 第30回日本疼痛学会
  • Place of Presentation: 福岡
• [Presentation] 培養DRGニューロンにおけるNGF刺激下でのASIC3およびTRPV1mRNAの発現変化 (2008)
  • Author(s): 松岡和義、大森恵、板野義太郎、横山正尚
  • Organizer: 第30回日本疼痛学会
  • Place of Presentation: 福岡
• [Presentation] EXPRESSION OF ASIC3 AND TRPV1 IN CULTURED RAT DRG NEURONS STIMULATED WITH NGF (2008)
  • Author(s): Matsuoka K, Yokoyama M, et al
  • Organizer: 12th World Congress on Pain
  • Place of Presentation: Glasgow, UK
• [Presentation] Incidence of traumatic cerebrospinal fluid leak following whiplash associated disorders (2008)
  • Author(s): Ishikawa s, Omori M, et al
  • Organizer: 12th World Congress on Pain
  • Place of Presentation: Glasgow, UK
• [Presentation] Effects of selective spinal nerve ligation on acetic acid-induced nociceptive responses and ASIC3 immunoreactivity in the rat dorsal root ganglion (2008)
  • Author(s): Omori M, Yokoyama M, et al
  • Organizer: 12th World Congress on Pain
  • Place of Presentation: Glasgow, UK
• [Presentation] Effects of NGF on Expression of ASIC3 and TRPVl ill Cultured Rat DRG Neurons (2008)
  • Author(s): Matsuoka Y, Yokovama M, et al
  • Organizer: American Societv of Anesthesiologists
  • Place of Presentation: Orlando, USA
• [Presentation] Effects of Selective Spinal Nerve Ligation on Acetic Acid-induced Nociceptive Responses (2008)
  • Author(s): Yokoyama M. Omori H, et al
  • Organizer: American Society of Anesthesiologists
  • Place of Presentation: Orlando, USA
• [Presentation] 脊髄神経傑作が酢酸刺激による疼痛行動に及ぼす変化に関する研究 (2008)
  • Author(s): 大森恵, 横山正尚, 他
  • Organizer: 弟30回日本疼痛学会
  • Place of Presentation: 福岡
• [Presentation] 培養DRGニューロンにおけるNGF刺激下でのASIC3およびTRPVlmRNAの発現変化 (2008)
  • Author(s): 松岡義和, 横山正尚, 他
  • Organizer: 弟30回日本疼痛学会
  • Place of Presentation: 福岡
• [Presentation] IV PCA 持続注入法・による術後鎮痛 : モルヒネIV PCA (2008)
  • Author(s): 横山正尚, 中塚秀輝, 他
  • Organizer: 第28回日本臨床麻酔学会
  • Place of Presentation: 京都
• [Presentation] ASIC3 Expression in Dorsal Root Ganglion by L5 Spinal Nerve Ligation in Rats (2007)
  • Author(s): Omori M, Yokoyama M, et. al.
  • Organizer: American Society of Anesthesiologists Annual Meting
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2007-10-14
• [Presentation] Brain-Derived Neurotrophic Factor Splice-Variants in the Cultured Neuron from the Rat DRG (2007)
  • Author(s): Matsuoka Y, Yokoyama M, et. al.
  • Organizer: American Society of Anesthesiologists Annual Meting
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2007-10-14
• [Presentation] 慢性頭痛モデルにおけるラット後根神経節のASIC3発現に関する研究 (2007)
  • Author(s): 大森恵、横山正尚
  • Organizer: 第20回日本疼痛学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-07-07
• [Presentation] ラット後根神経節およびセルラインにおけるBDNFmRNAスプライトバリアントの発現様式 (2007)
  • Author(s): 松岡義和、横山正尚、他
  • Organizer: 第54回日本麻酔科学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-05-31
• [Presentation] 炎症性頭痛モデルと神経因性疼痛モデルのDRGにおけるmultiple BDNF transcriptsおよびBDNFタンパクの発現様式 (2007)
  • Author(s): 小林浩之、横山正尚、他
  • Organizer: 第54回日本麻酔科学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-05-31