A new pain regulation systems activated by the crosstalk between brain striatum and neuropeptides

• Project/Area Number: 15K08233
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Hiroshima University
• Principal Investigator: Nakata Yoshihiro 広島大学, 医歯薬保健学研究科(薬), 名誉教授 (40133152)
• Co-Investigator(Kenkyū-buntansha): 森岡 徳光 広島大学, 医歯薬保健学研究科(薬), 教授 (20346505)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Substance P / Striatum / Volume transmitter / Pain / volume transmission / 線条体 / 神経障害性疼痛 / volume transmitter / サブスタンスＰ / 神経障害性疼痛モデルラット / substance P / 脳線条体 / リバースマイクロダイアリシス法

Outline of Final Research Achievements

The striatum is involved in not only the modulation of motor functioning but also in nociceptive processing. One brain nucleus that could be a projection target of striatal neurons is the rostral ventromedial medulla (RVM). Peripheral nociceptive stimulation induces a slow-on set substance P (SP) release as a volume transmitter and evokes phosphorylation of ERK by the NK-1 receptor activation.
Continuous striatal infusion of SP by the reverse microanalysis method diffuses with extra low concentration of SP into the striatum and likely to mimic volume transmission. In present study, the data demonstrated that the activation of the SP-volume transmission but not wired transmission in the striatum attenuated tissue injury-induced nociception using neuropathic pain model rats.These observations suggest that the modulation of the SP volume transmission system in the striatum could be a potent therapeutic target for patients with chronic pain due to neurological disorders.

Research Products

• [Presentation] 脳線条体におけるdopamine-substance P系を介した疼痛抑制メカニズムの解明 (2017)
  • Author(s): 岸田 祐輝、中村 庸輝、中島 一恵、仲田 義啓、森岡 徳光
  • Organizer: 第 56 回 日本薬学会・日本薬剤師会・日本病院薬剤師会
• [Presentation] 慢性疼痛時での脳線条体substance Pを介した疼痛制御機構 (2016)
  • Author(s): 福重 亮, 中村庸輝, 森岡徳光, 仲田義啓
  • Organizer: 第129回日本薬理学会近畿部会
  • Place of Presentation: 広島市
  • Year and Date: 2016-06-24
• [Presentation] 脳線条体へのsubstance P持続投与により誘発される疼痛制御機構の解明 (2016)
  • Author(s): 福重 亮, 中村庸輝, 森岡徳光, 仲田義啓
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-24
• [Presentation] Involvement of the striatal substance P nervous system in regulation of nociceptive transmission. (2016)
  • Author(s): 福重 亮, 中村庸輝, 森岡徳光, 仲田義啓
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-10
• [Presentation] 線条体サブスタンスＰ神経系による疼痛抑制作用のメカニズム (2015)
  • Author(s): 渡部亨平、福重 亮、岸田祐輝、中村庸輝 森岡徳光、仲田義啓
  • Organizer: 第128回 日本薬理学会近畿部会
  • Place of Presentation: 吹田市
  • Year and Date: 2015-11-20
• [Presentation] 線条体サブスタンスＰ神経系の疼痛抑制作用とドーパミン神経系との関係 (2015)
  • Author(s): 渡部亨平、福重 亮、岸田祐輝、中村庸輝 森岡徳光、仲田義啓
  • Organizer: 第 54 回 日本薬学会・日本薬剤師会・日本病院薬剤師会
  • Place of Presentation: 高知市
  • Year and Date: 2015-10-31
• [Presentation] 神経障害性疼痛モデルラットにおける脳線条体substance P神経系を介した疼痛制御機構 (2015)
  • Author(s): 福重 亮, 中村庸輝, 森岡徳光, 仲田義啓
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2015
  • Place of Presentation: 東京都
  • Year and Date: 2015-08-30