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Research ArticleNEUROPHARMACOLOGY

Spinal d-Amino Acid Oxidase Contributes to Neuropathic Pain in Rats

Wen-Juan Zhao, Zhen-Yu Gao, Hong Wei, Hui-Zhen Nie, Qian Zhao, Xiang-Jun Zhou and Yong-Xiang Wang
Journal of Pharmacology and Experimental Therapeutics January 2010, 332 (1) 248-254; DOI: https://doi.org/10.1124/jpet.109.158816
Wen-Juan Zhao
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Zhen-Yu Gao
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Hong Wei
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Hui-Zhen Nie
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Qian Zhao
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Xiang-Jun Zhou
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Yong-Xiang Wang
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Abstract

d-Amino acid oxidase (DAO) is an enzyme catalyzing oxidative deamination of neutral and polar d-amino acids and is expressed in the kidneys, liver, and central nervous system (CNS) including the spinal cord. We have previously demonstrated that DAO gene deletion/mutation by using mutant ddY/DAO(−/−) mice and systemic administration of the DAO inhibitor sodium benzoate blocked formalin-induced hyperalgesia in mice. In this study, we further investigated the potential role of DAO in neuropathic pain in a rat model of tight L5/L6 spinal nerve ligation. After L5/L6 spinal nerve ligation, the mRNA expression (measured by real-time quantitative polymerase chain reaction) and enzyme activity (measured by a colorimetric method) of DAO in the lumbar spinal cord were markedly increased, in agreement with the development of neuropathic pain (mechanical allodynia). Intraperitoneal injection of sodium benzoate (400 mg/kg) specifically blocked mechanical allodynia in neuropathic rats and formalin-induced hyperalgesia but did not suppress acute pain responses in the tail-flick test or formalin test. Systemic injection of sodium benzoate also inhibited DAO activity in the lumbar spinal cord of rats. Furthermore, direct intrathecal (spinal cord) injection of benzoate (30 μg/rat) specifically blocked spinal nerve ligation-induced mechanical allodynia in neuropathic rats and formalin-induced hyperalgesia (but not acute pain) in the formalin test. Based on the above results, we conclude that spinal DAO plays a pronociceptive (rather than an antinociceptive) role and might be a target molecule for the treatment of chronic pain of neuropathic origin.

Footnotes

  • This work was supported by the Mega New Drug Development Program of China [Grant 2009ZX09301-007]; and the New Doctoral Scholars Foundation from the Ministry of Education of China [Grant 200802481107].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.109.158816

  • ABBREVIATIONS:

    DAO
    d-amino acid oxidase
    CNS
    central nervous system
    PCR
    polymerase chain reaction
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    Ct
    cycle threshold
    ANOVA
    analysis of variance
    AS057278
    5-methylpyrazole-3-carboxylic acid
    NMDA
    N-methyl-d-aspartate.

    • Received July 13, 2009.
    • Accepted October 13, 2009.
  • © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 332 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 332, Issue 1
1 Jan 2010
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Research ArticleNEUROPHARMACOLOGY

Spinal d-Amino Acid Oxidase Contributes to Neuropathic Pain in Rats

Wen-Juan Zhao, Zhen-Yu Gao, Hong Wei, Hui-Zhen Nie, Qian Zhao, Xiang-Jun Zhou and Yong-Xiang Wang
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 248-254; DOI: https://doi.org/10.1124/jpet.109.158816

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Research ArticleNEUROPHARMACOLOGY

Spinal d-Amino Acid Oxidase Contributes to Neuropathic Pain in Rats

Wen-Juan Zhao, Zhen-Yu Gao, Hong Wei, Hui-Zhen Nie, Qian Zhao, Xiang-Jun Zhou and Yong-Xiang Wang
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 248-254; DOI: https://doi.org/10.1124/jpet.109.158816
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