Analgesia mediated by enhancement of descending noradrenergic neuron with GDNF

2012 Fiscal Year Final Research Report

• 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
• Keywords: 神経障害性疼痛 / GDNF / 下行性疼痛抑制 / ノルアドレナリン

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] 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 Pages: 1047-1057
  • DOI: 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: J Nippon Med Sch Volume: 79 Pages: 129-138
  • DOI: doi:10.1272/jnms.79.129
  • 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 Pages: e32268
  • DOI: 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: J Pharmacol Sci Volume: 117 Pages: 180-188
  • DOI: doi:10.1254/jphs.11116FP
  • 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 Pages: 163-168
  • DOI: 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 Pages: 1130-1139
  • DOI: 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 Pages: 35-43
  • DOI: 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
  • DOI: doi:10.1186/1744-8069-7-2
  • 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
• [Journal Article] Nerve injury-induced upregulation of miR-21 in the primary sensory neurons contributes to neuropathic pain in rats.
  • Author(s): Sakai A,Suzuki H.
  • Journal Title: Biochem Biophys Res Commun
  • DOI: DOI:10.1016/j.bbrc.2013.04.089
  • Peer Reviewed
• [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
  • Year and Date: 20110300
• [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