Peripheral-Type Benzodiazepine Receptor Antagonist Is Effective in Relieving Neuropathic Pain in Mice
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概要
- 論文の詳細を見る
cDNA microarray analysis showed the expression of peripheral-type benzodiazepine receptor (PBR) mRNA is slightly enhanced in the spinal cord of mice with spinal nerve injury (SNL) as compared with sham-operated mice. PBR transports cholesterol to the mitochondria, where cholesterol is converted to pregnenolone. Pregnenolone is then metabolized to progesterone, an activator of progesterone receptor, and further metabolized to produce allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC), positive allosteric modulators and activators of the GABAA receptor. In the present study, we first tested whether the enhanced PBR expression is causally related to neuropathic pain, and we found that the PBR antagonist PK11195 is effective in reducing SNL-induced mechanical allodynia and thermal hyperalgesia. Next we tested whether the PK11195-induced antinociception is attributable to reduced neurosteroid synthesis, which may possibly lead to reduced activation of the progesterone receptor and/or GABAA receptor. We found that allopregnanolone and 3α,5α-THDOC are effective in reducing the anti-hyperalgesic effect of PK11195, suggesting a partial contribution of reduced GABAA-receptor activation to PK11195-induced antinociception.
- 2009-05-20
著者
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KURIHARA Takashi
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental U
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TAKASAKI Ichiro
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceu
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Tanabe Tsutomu
Department Of Pharmacology And Neurobiology Graduate School Of Medicine Tokyo Medical And Dental Uni
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Takasaki Ichiro
Department Of Pharmacology And Neurobiology Graduate School Of Medicine Tokyo Medical And Dental Uni
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Tanabe Tsutomu
Department Of Pharmacology And Neurobiology Graduate School Of Medicine Tokyo Medical And Dental Uni
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Kondo Daisuke
Department Of Pharmacology And Neurobiology Graduate School Of Medicine Tokyo Medical And Dental Uni
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Kondo Daisuke
Department Of Chemical Reaction Engineering Nagoya City University
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Saegusa Hironao
Department Of Pharmacology And Neurobiology Graduate School Of Medicine Tokyo Medical And Dental Uni
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YABE Ritsuko
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental U
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ZONG Shuqin
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental U
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Zong Shuqin
Department Of Pharmacology And Neurobiology Graduate School Of Medicine Tokyo Medical And Dental Uni
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Yabe Ritsuko
Department Of Pharmacology And Neurobiology Graduate School Of Medicine Tokyo Medical And Dental Uni
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Kurihara Takashi
Department Of Pharmacology And Neurobiology Graduate School Of Medicine Tokyo Medical And Dental Uni
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- Peripheral-Type Benzodiazepine Receptor Antagonist Is Effective in Relieving Neuropathic Pain in Mice
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