Analgesia mediated by enhancement of descending noradrenergic neuron with GDNF

• Project/Area Number: 22791457
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Nippon Medical School
• Principal Investigator: SAKAI Atsushi 日本医科大学, 医学部, 助教 (30386156)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 神経障害性疼痛 / GDNF / 下行性疼痛抑制 / ノルアドレナリン / 青斑核

Research Abstract

Administration of substance P into locus coeruleus, a nucleus constituting descending noradrenergic neurons, attenuated neuropathic pain via NK1 receptor activation. In addition, administration of glial cell line-derived neurotrophic factor (GDNF) into the locus coeruleus persistently attenuated the neuropathic pain. These analgesic effects were mediated by noradrenergic descending inhibition.

Research Products

• [Journal Article] Nerve injury-induced upregulation of miR-21 in the primary sensory neurons contributes to neuropathic pain in rats. (2013)
  • Author(s): Sakai A,Suzuki H.
  • Journal Title: Biochem Biophys Res Commun Volume: 435 Issue: 2 Pages: 176-181
  • DOI: 10.1016/j.bbrc.2013.04.089
  • Peer Reviewed
• [Journal Article] Activation of NK1 receptors in the locus coeruleus induces analgesia through noradrenergic-mediated descending inhibition in a rat model of neuropathic pain. (2012)
  • Author(s): Muto Y, Sakai A, Sakamoto A, Suzuki H.
  • Journal Title: Br J Pharmacol Volume: 166 Issue: 3 Pages: 1047-1057
  • DOI: 10.1111/j.1476-5381.2011.01820.x
  • Peer Reviewed
• [Journal Article] Involvement of Tachykinins and NK₁ Receptor in the Joint Inflammation with Collagen Type II-Specific Monoclonal Antibody-Induced Arthritis in Mice (2012)
  • Author(s): Makino A, Sakai A, Ito H, Suzuki H.
  • Journal Title: Journal of Nippon Medical School Volume: 79 Issue: 2 Pages: 129-138
  • DOI: 10.1272/jnms.79.129
  • NAID: 130004147152
  • ISSN: 1345-4676, 1347-3409
  • Peer Reviewed
• [Journal Article] Hemokinin-1 gene expression is upregulated in microglia activated by lipopolysaccharide through NF-κB and p38 MAPK signaling pathways. (2012)
  • Author(s): Sakai A, Takasu K, Sawada M, Suzuki H.
  • Journal Title: PLoS ONE Volume: 7 Issue: 2 Pages: e32268-e32268
  • DOI: 10.1371/journal.pone.0032268
  • Peer Reviewed
• [Journal Article] Suppressive Effects of Glycyrrhetinic Acid Derivatives on Tachykinin Receptor Activation and Hyperalgesia (2011)
  • Author(s): Akasaka Y, Sakai A, Takasu K, Tsukahara M, Hatta A, Suzuki H, Inoue H.
  • Journal Title: Journal of Pharmacological Sciences Volume: 117 Issue: 3 Pages: 180-188
  • DOI: 10.1254/jphs.11116FP
  • NAID: 10030453357
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Journal Article] Intra-articular administration of tachykinin NK_1 receptor antagonists reduces hyperalgesia and cartilage destruction in the inflammatory joint in rats with adjuvant-induced arthritis. (2011)
  • Author(s): Uematsu T, Sakai A, Ito H, Suzuki H.
  • Journal Title: Eur J Pharmacol Volume: 668 Issue: 1-2 Pages: 163-168
  • DOI: 10.1016/j.ejphar.2011.06.037
  • Peer Reviewed
• [Journal Article] Overexpression of GDNF in the uninjured DRG exerts analgesic effectson neuropathic pain following segmental spinal nerve ligation in mice. (2011)
  • Author(s): Takasu K, Sakai A, Hanawa H, Shimada T, Suzuki H.
  • Journal Title: J Pain Volume: 12 Issue: 11 Pages: 1130-1139
  • DOI: 10.1016/j.jpain.2011.04.003
  • Peer Reviewed
• [Journal Article] A subset of μ -opioid receptor-expressing cells in the rostral ventromedial medulla contribute to thermal hyperalgesia in experimental neuropathic pain. (2011)
  • Author(s): Mase H, Sakai A, Sakamoto A, Suzuki H.
  • Journal Title: Neurosci Res Volume: 70 Issue: 1 Pages: 35-43
  • DOI: 10.1016/j.neures.2011.01.003
  • Peer Reviewed
• [Journal Article] A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain (2011)
  • Author(s): Toda S, Sakai A, Ikeda Y, Sakamoto A, Suzuki H.
  • Journal Title: Mol Pain Volume: 7 Pages: 2-2
  • DOI: 10.1186/1744-8069-7-2
  • Peer Reviewed
• [Journal Article] A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain (2011)
  • Author(s): Shigeru Toda
  • Journal Title: Molecular Pain Volume: 7 Pages: 2-2
  • Peer Reviewed
• [Journal Article] miR-7a alleviates chronic neuropathic pain through regulation of neuronal excitability.
  • Author(s): Sakai A, Saitow F, Miyake N, Miyake K, Shimada T, Suzuki H.
  • Journal Title: Brain
  • Peer Reviewed
• [Presentation] 神経障害性疼痛モデルラットの傷害DRG神経におけるmicroRNAの発現低下 (2012)
  • Author(s): 坂井敦
  • Organizer: 日本薬理学会年会
  • Place of Presentation: 国立京都国際会館・グランドプリンスホテル京都
  • Year and Date: 2012-03-14
• [Presentation] Distinct expression changes of microRNAs in the dorsal rootganglion in the time course of neuropathic pain (2011)
  • Author(s): Atsushi Sakai
  • Organizer: Cell Symposia : Regulatory RNAs 2011
  • Place of Presentation: Wyndham Hotel, Chicago
  • Year and Date: 2011-10-12
• [Presentation] 青斑核におけるNK-1受容体の活性化は下行性抑制を介して神経障害性疼痛を緩和する (2011)
  • Author(s): 武藤友美
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜.
  • Year and Date: 2011-09-17
• [Presentation] 神経障害性疼痛モデル動物の後根神経節におけるマイクロRNAの発現解析 (2011)
  • Author(s): 坂井敦
  • Organizer: 日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-09-17
• [Presentation] 青斑核におけるNK-1受容体の活性化は下行性抑制を介して神経障害性疼痛を緩和する (2011)
  • Author(s): 武藤友美
  • Organizer: 日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-09-17
• [Presentation] 神経障害性疼痛モデルラットにおける青斑核へのサブスタンスP投与による鎮痛効果 (2011)
  • Author(s): 武藤友美
  • Organizer: 日本麻酔科学会第58回学術集会
  • Place of Presentation: 神戸ポートピアホテル・神戸国際展示場.
  • Year and Date: 2011-05-20
• [Presentation] 神経障害性疼痛モデルラットにおける青斑核へのサブスタンスP投与による鎮痛効果 (2011)
  • Author(s): 武藤友美
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 神戸ポートピアホテル・神戸国際展示場
  • Year and Date: 2011-05-20
• [Presentation] サブスタンスPの青斑核への投与は神経障害性疼痛を抑制する (2011)
  • Author(s): 坂井敦
  • Organizer: 日本薬理学会年会
  • Place of Presentation: パシフィコ横浜(誌上開催)
  • Year and Date: 2011-03-23
• [Presentation] 活性化マイクログリアにおけるタキキニン遺伝子TAC4の発現上昇 (2011)
  • Author(s): 高須久望子
  • Organizer: 日本薬理学会年会
  • Place of Presentation: パシフィコ横浜(誌上開催)
  • Year and Date: 2011-03-22
• [Presentation] サブスタンスPの青斑核への投与は神経障害性疼痛を抑制する (2011)
  • Author(s): 坂井敦
  • Organizer: 第84回日本薬理学会年会
• [Presentation] 非損傷DRGにおけるGDNFの過剰発現は神経障害性疼痛を緩和する (2010)
  • Author(s): 高須久望子
  • Organizer: 日本薬理学会関東部会
  • Place of Presentation: 自治医科大学地域医療情報研修センター
  • Year and Date: 2010-10-23
• [Presentation] 局所麻酔薬ロピバカインは神経障害性疼痛における活性化脊髄グリア細胞を抑制する (2010)
  • Author(s): 坂井敦
  • Organizer: 日本神経科学学会・日本神経化学学会・日本神経回路学会合同大会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2010-09-02
• [Presentation] ロピバカインはNGFの発現上昇を介して神経因性疼痛を緩和する (2010)
  • Author(s): 戸田繁
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2010-06-03
• [Presentation] Rostral ventromedial medullaへのカイニン酸投与は神経障害性疼痛における熱性痛覚過敏を減弱させる (2010)
  • Author(s): 間瀬大司
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 福岡国際会議揚
  • Year and Date: 2010-06-03
• [Presentation] miR-7a overexpression in the DRG neurons suppresses neuropathic pain without affecting physiological and inflammatory pain
  • Author(s): 坂井 敦
  • Organizer: 日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] miR-7a alleviates the maintenance of neuropathic pain by regulating the voltage-gated sodium channel β2 subunit
  • Author(s): 坂井 敦
  • Organizer: 日本薬理学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 青斑核へのグリア細胞株由来神経栄養因子の投与はノルアドレナリンによる下行性抑制を介して神経障害性疼痛を緩和する
  • Author(s): 木村 茉莉子
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 札幌プリンスホテル