ArticleJournal of neurophysiology2010
Impaired glial glutamate uptake induces extrasynaptic glutamate spillover in the spinal sensory synapses of neuropathic rats.
Article in Journal of neurophysiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 81 citations in OpenAlex.
- Targeting Spinal Dorsal Horn Sensitisation in Chronic Pain: Mechanisms and Translational Strategies.Neuroscience bulletin · 2026Review
- Structural reorganization of medullary dorsal horn astrocytes in a rat model of neuropathic pain.Brain structure & function · 2024Article
- Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Dysregulation of sphingolipid metabolism in pain.Frontiers in pharmacology · 2024Review
- Real-time in vivo thoracic spinal glutamate sensing during myocardial ischemia.American journal of physiology. Heart and circulatory physiology · 2023Article
- Review
- Roles of Phosphorylation of N-Methyl-D-Aspartate Receptor in Chronic Pain.Cellular and molecular neurobiology · 2023Review
- Increase of glutamate in satellite glial cells of the trigeminal ganglion in a rat model of craniofacial neuropathic pain.Frontiers in neuroanatomy · 2023Article
- Metformin inhibits spontaneous excitatory postsynaptic currents in spinal dorsal cord neurons from paclitaxel-treated rats.Frontiers in synaptic neuroscience · 2023Article
- The Acute Antiallodynic Effect of Tolperisone in Rat Neuropathic Pain and Evaluation of Its Mechanism of Action.International journal of molecular sciences · 2022Article
- Article
- Sensitization of supra-threshold pain responses-Translational aspects and mechanisms.Frontiers in network physiology · 2022Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Article
- Synergistic interaction between trazodone and gabapentin in rodent models of neuropathic pain.PloS one · 2021Article
- Ceftriaxone Relieves Trigeminal Neuropathic Pain Through Suppression of Spatiotemporal Synaptic PlasticityFrontiers in cellular neuroscience · 2020Article
- An integrated review on new targets in the treatment of neuropathic pain.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Review
- Higher ambient synaptic glutamate at inhibitory versus excitatory neurons differentially impacts NMDA receptor activity.Nature communications · 2018Article
- Potentiation of spinal glutamatergic response in the neuron-glia interactions underlies the intrathecal IL-1β-induced thermal hyperalgesia in rats.CNS neuroscience & therapeutics · 2017Article
- NMDA receptors: linking physiological output to biophysical operation.Nature reviews. Neuroscience · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glial cell dysfunction and excessive glutamate receptor activation in spinal dorsal horn neurons are hallmark mechanisms of pathological pain. The way in which glial cell dysfunction leads to excessive glutamate receptor activation in the spinal sensory synapses remains unknown. We and others recently reported the downregulation of glial glutamate transporter (GT) protein expression in the spinal dorsal horn of neuropathic rats. In this study, we showed that excitatory postsynaptic currents originating from N-methyl-d-aspartate receptor activation (NMDA EPSCs) elicited by peripheral synaptic input in the spinal sensory synapses were enhanced in neuropathic rats with mechanical allodynia induced by partial sciatic nerve ligation. The enhanced NMDA EPSCs were accompanied by an increased proportion of NR2B receptor activation. Physically blocking the extrasynaptic glutamate with dextran or chemically scavenging the glutamate with glutamic-pyruvic transaminase ameliorated the abnormal NMDA EPSCs in neuropathic rats. Pharmacological blockade of glial GTs with dihydrokainic acid enhanced NMDA receptor activation elicited by synaptic input or puffed glutamate in normal control rats, but this effect was precluded in neuropathic rats. Thus extrasynaptic glutamate spillover and extrasynaptic NMDA receptor activation induced by deficient glial glutamate uptake in the synapses resulted in the excessive activation of NMDA receptors in neuropathic rats. It is suggested that extrasynaptic glutamate spillover may be a key synaptic mechanism related to phenotypic alterations induced by nerve injury in the spinal dorsal horn and that glial GTs are potential new targets in the development of analgesics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.