Show simple item record

dc.contributor.authorWatanabe, Moe
dc.contributor.authorSugiura, Yuki
dc.contributor.authorSugiyama, Eiji
dc.contributor.authorNarita, Michiko
dc.contributor.authorNavratilova, Edita
dc.contributor.authorKondo, Takashige
dc.contributor.authorUchiyama, Naohiko
dc.contributor.authorYamanaka, Akihiro
dc.contributor.authorKuzumaki, Naoko
dc.contributor.authorPorreca, Frank
dc.contributor.authorNarita, Minoru
dc.date.accessioned2018-03-27T22:44:38Z
dc.date.available2018-03-27T22:44:38Z
dc.date.issued2018-01-08
dc.identifier.citationExtracellular N-acetylaspartylglutamate released in the nucleus accumbens modulates the pain sensation: Analysis using a microdialysis/mass spectrometry integrated system 2018, 14:174480691875493 Molecular Painen
dc.identifier.issn1744-8069
dc.identifier.issn1744-8069
dc.identifier.pmid29310499
dc.identifier.doi10.1177/1744806918754934
dc.identifier.urihttp://hdl.handle.net/10150/627130
dc.description.abstractVarious 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.
dc.description.sponsorshipMEXT-Supported Program for the Strategic Research Foundation at Private Universities [S1411019]; JSPS [26293346, 16748651]en
dc.language.isoenen
dc.publisherSAGE PUBLICATIONS INCen
dc.relation.urlhttp://journals.sagepub.com/doi/10.1177/1744806918754934en
dc.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.en
dc.subjectPainen
dc.subjectanalgesiaen
dc.subjectmorphineen
dc.subjectnucleus accumbensen
dc.subjectdopamineen
dc.subjectoptogeneticsen
dc.subjectimaging mass spectrometryen
dc.subjectin vivo microdialysisen
dc.subjectmass spectrometryen
dc.subjectN-acetylaspartylglutamateen
dc.titleExtracellular N-acetylaspartylglutamate released in the nucleus accumbens modulates the pain sensation: Analysis using a microdialysis/mass spectrometry integrated systemen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Pharmacol, Arizona Hlth Sci Ctren
dc.identifier.journalMolecular Painen
dc.description.noteOpen access journal.en
dc.description.collectioninformationThis 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.en
dc.eprint.versionFinal published versionen
dc.contributor.institutionDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan
dc.contributor.institutionDepartment of Biochemistry, Keio University School of Medicine, Tokyo, Japan
dc.contributor.institutionDepartment of Biochemistry, Keio University School of Medicine, Tokyo, Japan
dc.contributor.institutionDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan
dc.contributor.institutionDepartment of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ, USA
dc.contributor.institutionDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan
dc.contributor.institutionDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan
dc.contributor.institutionDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
dc.contributor.institutionDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan
dc.contributor.institutionDepartment of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ, USA
dc.contributor.institutionDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan
refterms.dateFOA2018-09-12T07:05:14Z
html.description.abstractVarious 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.


Files in this item

Thumbnail
Name:
1744806918754934.pdf
Size:
1.081Mb
Format:
PDF
Description:
Final Published Version

This item appears in the following Collection(s)

Show simple item record