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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/627130 |
| Date | 08 January 2018 |
| Creators | Watanabe, Moe, Sugiura, Yuki, Sugiyama, Eiji, Narita, Michiko, Navratilova, Edita, Kondo, Takashige, Uchiyama, Naohiko, Yamanaka, Akihiro, Kuzumaki, Naoko, Porreca, Frank, Narita, Minoru |
| Contributors | Univ Arizona, Dept Pharmacol, Arizona Hlth Sci Ctr, Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan, Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan, Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan, Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan, Department of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ, USA, Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan, Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan, Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan, Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan, Department of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ, USA, Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan |
| Publisher | SAGE PUBLICATIONS INC |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| 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. |
| Relation | http://journals.sagepub.com/doi/10.1177/1744806918754934 |
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