The search for novel analgesics based on pain control with aromatase and GPR30

• Project/Area Number: 26462387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: National Center for Global Health and Medicine (2016-2017); National Cancer Center Japan (2014-2015)
• Principal Investigator: Shiraishi Seiji 国立研究開発法人国立国際医療研究センター, その他部局等, 医師 (90216177)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: GPR30 / aromatase / ovariectomy / miRNA / アロマターゼ / 疼痛 / 神経障害性疼痛 / ミクログリア / エストロゲン

Outline of Final Research Achievements

Aromatase inhibitor(Letrozole,1 or 5 mg/kg) reduced threshold value of pain for a Formalin test, neuropathic pain (Seltzer model) and a cancer bone metastases pain model. G-protein-coupled estrogen receptor, GPR30 inhibitor (G15) of the cell membrane localization increased threshold value of pain for each animal models. We examined a manifestation immunohistochemically change of GPR30 and aromatase in the spinal cord in a neuropathic pain and a cancer pain mode rats. Athreshold value of pain decrease with the aromatase inhibitor administration less had the significant difference with the ovariectomy rat as a post-menopausal model. Using each spine fusion graft, we compared the microglial activation by the IBa1 immunostaining and examined association with the pain as compared with a control in each miRNA.