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    Extracellular N-acetylaspartylglutamate released in the nucleus accumbens modulates the pain sensation: Analysis using a microdialysis/mass spectrometry integrated system

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    Author
    Watanabe, Moe
    Sugiura, Yuki
    Sugiyama, Eiji
    Narita, Michiko
    Navratilova, Edita
    Kondo, Takashige
    Uchiyama, Naohiko
    Yamanaka, Akihiro
    Kuzumaki, Naoko
    Porreca, Frank
    Narita, Minoru
    Show allShow less
    Affiliation
    Univ Arizona, Dept Pharmacol, Arizona Hlth Sci Ctr
    Issue Date
    2018-01-08
    Keywords
    Pain
    analgesia
    morphine
    nucleus accumbens
    dopamine
    optogenetics
    imaging mass spectrometry
    in vivo microdialysis
    mass spectrometry
    N-acetylaspartylglutamate
    
    Metadata
    Show full item record
    Publisher
    SAGE PUBLICATIONS INC
    Citation
    Extracellular N-acetylaspartylglutamate released in the nucleus accumbens modulates the pain sensation: Analysis using a microdialysis/mass spectrometry integrated system 2018, 14:174480691875493 Molecular Pain
    Journal
    Molecular Pain
    Rights
    © The Author(s) 2018. Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons AttributionNonCommercial 4.0 License.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Various small molecules act as neurotransmitters and orchestrate neural communication. Growing evidence suggests that not only classical neurotransmitters but also several small molecules, including amino acid derivatives, modulate synaptic transmission. As conditions of acute and chronic pain alter neuronal excitability in the nucleus accumbens, we hypothesized that small molecules released in the nucleus accumbens might play important roles in modulating the pain sensation. However, it is not easy to identify possible pain modulators owing to the absence of a method for comprehensively measuring extracellular small molecules in the brain. In this study, through the use of an emerging metabolomics technique, namely ion chromatography coupled with high-resolution mass spectrometry, we simultaneously analyzed the dynamics of more than 60 small molecules in brain fluids collected by microdialysis, under both the application of pain stimuli and the administration of analgesics. We identified N-acetylaspartylglutamate as a potential pain modulator that is endogenously released in the nucleus accumbens. Infusion of N-acetylaspartylglutamate into the nucleus accumbens significantly attenuated the pain induced by the activation of sensory nerves through optical stimulation. These findings suggest that N-acetylaspartylglutamate released in the nucleus accumbens could modulate pain sensation.
    Note
    Open access journal.
    ISSN
    1744-8069
    1744-8069
    PubMed ID
    29310499
    DOI
    10.1177/1744806918754934
    Version
    Final published version
    Sponsors
    MEXT-Supported Program for the Strategic Research Foundation at Private Universities [S1411019]; JSPS [26293346, 16748651]
    Additional Links
    http://journals.sagepub.com/doi/10.1177/1744806918754934
    ae974a485f413a2113503eed53cd6c53
    10.1177/1744806918754934
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