Extracellular N-acetylaspartylglutamate released in the nucleus accumbens modulates the pain sensation: Analysis using a microdialysis/mass spectrometry integrated system
Author
Watanabe, MoeSugiura, Yuki
Sugiyama, Eiji
Narita, Michiko
Navratilova, Edita
Kondo, Takashige
Uchiyama, Naohiko
Yamanaka, Akihiro
Kuzumaki, Naoko
Porreca, Frank
Narita, Minoru
Affiliation
Univ Arizona, Dept Pharmacol, Arizona Hlth Sci CtrIssue Date
2018-01-08Keywords
Painanalgesia
morphine
nucleus accumbens
dopamine
optogenetics
imaging mass spectrometry
in vivo microdialysis
mass spectrometry
N-acetylaspartylglutamate
Metadata
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SAGE PUBLICATIONS INCCitation
Extracellular N-acetylaspartylglutamate released in the nucleus accumbens modulates the pain sensation: Analysis using a microdialysis/mass spectrometry integrated system 2018, 14:174480691875493 Molecular PainJournal
Molecular PainRights
© 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
1744-80691744-8069
PubMed ID
29310499Version
Final published versionSponsors
MEXT-Supported Program for the Strategic Research Foundation at Private Universities [S1411019]; JSPS [26293346, 16748651]Additional Links
http://journals.sagepub.com/doi/10.1177/1744806918754934ae974a485f413a2113503eed53cd6c53
10.1177/1744806918754934
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Except where otherwise noted, this item's license is described as © 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.