Peripheral-Type Benzodiazepine Receptor Antagonist Is Effective in Relieving Neuropathic Pain in Mice

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Author(s)

    • TAKASAKI Ichiro
    • Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University
    • KURIHARA Takashi
    • Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University
    • ZONG Shuqin
    • Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University
    • TANABE Tsutomu
    • Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University

Abstract

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 GABA<sub>A</sub> 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 GABA<sub>A</sub> 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 GABA<sub>A</sub>-receptor activation to PK11195-induced antinociception.<br>

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 110(1), 55-63, 2009-05-20

    The Japanese Pharmacological Society

References:  29

Cited by:  1

Codes

  • NII Article ID (NAID)
    10025736602
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13478613
  • NDL Article ID
    10225699
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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