ArticlePain2012
Peripheral nerve injury produces a sustained shift in the balance between glutamate release and uptake in the dorsal horn of the spinal cord.
Article in Pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- Targeting Spinal Dorsal Horn Sensitisation in Chronic Pain: Mechanisms and Translational Strategies.Neuroscience bulletin · 2026Review
- Spinal signatures of entrenched and treated neuropathic pain in male mice.Nature communications · 2026Article
- Neuroprotection and immunomodulation after treatment with NeuroBoost and NeuroHeal following ventral root crush in mice.IBRO neuroscience reports · 2026Article
- The effects of physical exercise on inflammation-induced maladaptive neuroplasticity in post-traumatic headache.Neuroscience · 2026Review
- The excitatory neurotransmitter glutamate and its receptors: the culprits behind neuropathic pain?Frontiers in aging neuroscience · 2026Review
- The Crosstalk Between Brain Energy Metabolism and Neuropathic Pain: Mechanisms and Therapeutic Implications.Metabolites · 2025Review
- Enhanced Anti-Nociception by Novel Dual Antagonists for 5-HT2AR and mGluR5 in Preclinical Models of Pain.Biomolecules · 2025Article
- Loss of Glutaminase 1 in Small Sensory Neurons Prevents Nerve Injury Induced Mechanical Allodynia: Insights From Conditional Knockout Mice.European journal of pain (London, England) · 2025Article
- Unmasking the relationship between CGRP and glutamate: from peripheral excitation to central sensitization in migraine.The journal of headache and pain · 2025Review
- Glial Modulator Antibiotics for Neuropathic Pain: Current Insights and Future Directions.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Action potential-independent spontaneous microdomain CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Real-time in vivo thoracic spinal glutamate sensing during myocardial ischemia.American journal of physiology. Heart and circulatory physiology · 2023Article
- Ac4C Enhances the Translation Efficiency of Vegfa mRNA and Mediates Central Sensitization in Spinal Dorsal Horn in Neuropathic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Alleviation of neuropathic pain with neuropeptide Y requires spinal Npy1r interneurons that coexpress Grp.JCI insight · 2023Article
- Non-response to first-line hormonal treatment for symptomatic endometriosis: overcoming tunnel vision. A narrative review.BMC women's health · 2023Review
- CaInternational journal of molecular sciences · 2023Article
- Protocol for Evaluating In Vivo the Activation of the P2RX7 Immunomodulator.Biological procedures online · 2023Article
- Exercise facilitates regeneration after severe nerve transection and further modulates neural plasticity.Brain, behavior, & immunity - health · 2022Article
- Spinal neuropeptide Y Y1 receptor-expressing neurons are a pharmacotherapeutic target for the alleviation of neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Glutamatergic systems in neuropathic pain and emerging non-opioid therapies.Pharmacological research · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Peripheral nerve injury provokes heightened excitability of primary sensory afferents including nociceptors, and elicits ectopic activity in lesioned and neighboring intact nerve fibers. The major transmitter released by sensory afferents in the superficial dorsal horn of the spinal cord is glutamate. Glutamate is critically involved in nociceptive signaling and the development of neuropathic pain. We recorded miniature excitatory postsynaptic currents (mEPSCs) from neurons in lamina II of the rat dorsal horn to assess spontaneous synaptic activity after spared nerve injury (SNI), a model of chronic neuropathic pain. Following SNI, the frequency of mEPSCs doubled, indicating heightened glutamate release from primary afferents or spinal interneurons. Consistent with this finding, glutamate concentrations in the cerebrospinal fluid were elevated at 1 and 4 weeks after SNI. Transmitter uptake was insufficient to prevent the rise in extracellular glutamate as the expression of glutamate transporters remained unchanged or decreased. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride, an antagonist of metabotropic glutamate receptor 5 (mGluR5), reduced the frequency of mEPSCs to its preinjury level, suggesting a positive feedback mechanism that involves facilitation of transmitter release by mGluR5 activation in the presence of high extracellular glutamate. Treatment with the β-lactam antibiotic ceftriaxone increased the expression of glutamate transporter 1 (Glt1) in the dorsal horn after SNI, raised transmitter uptake, and lowered extracellular glutamate. Improving glutamate clearance prevented the facilitation of transmitter release by mGluR5 and attenuated neuropathic pain-like behavior. Balancing glutamate release and uptake after nerve injury should be an important target in the management of chronic neuropathic pain.
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What OpenQuestion holds
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.