ArticlePain reports2026
3-Nitrotyrosine activates excitatory interneurons by inhibiting GABA receptors in the rat spinal dorsal horn.
Article in Pain reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: 3-Nitrotyrosine (3-NT) is a stable biomarker formed when reactive nitrogen species (RNS) interact with tyrosine residues. Emerging evidence suggests that RNS can amplify pain and contribute to chronic pain conditions. However, 3-NT is considered a relatively stable byproduct, and its role in pain mechanisms has not been thoroughly investigated. Objective: This study was conducted to investigate the effect of 3-NT in spinal dorsal horn neurons. Methods: We evaluated the effects of 3-NT on spontaneous excitatory postsynaptic currents (sEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in spinal dorsal horn neurons from male Sprague-Dawley rats. Blind whole-cell patch-clamp recordings were performed on transverse slices prepared from the isolated lumbosacral spinal cord. Results: Perfusion of 3-NT increased the frequency and amplitude of sEPSCs in spinal horn neurons in a concentration-dependent manner. However, 6-cyano-7-nitroquinoxaline-2,3-dione, an AMPA/kainate receptor antagonist, blocked the enhancement of sEPSCs by 3-NT. In addition, 3-NT administration had no effect on the frequency and amplitude of miniature EPSCs (mEPSCs) in the presence of tetrodotoxin , a sodium channel blocker. Conversely, 3-NT decreased the amplitude of mIPSCs in the presence of tetrodotoxin. 3-Nitrotyrosine decreased the amplitude of mIPSCs when strychnine, a glycine receptor antagonist, was present. However, in the presence of bicuculline, a GABA Conclusion: 3-Nitrotyrosine increases spontaneous glutamate release from the presynaptic terminal to spinal dorsal horn neurons by inhibiting GABA receptors on excitatory interneurons, which in turn enhances their activity.
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