ArticleCell reports2016
Chloride Homeostasis Critically Regulates Synaptic NMDA Receptor Activity in Neuropathic Pain.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 94 citations in OpenAlex.
- Restoration of gamma-aminobutyric acid homeostasis: A novel approach to alleviating central nervous system injury-associated immunodepression syndrome.Neural regeneration research · 2026Article
- HIV-1 gp120 Induces Nociceptive Hypersensitivity via α2δ-1-Bound NMDA Receptors at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- FOXA2 regulated by HDAC3-mediated deacetylation attenuates neuropathic pain by modulating microglial lipid metabolism and synaptic pruning dysregulation.Journal of neuroinflammation · 2025Article
- Article
- Tonic GABA and Glycine Inhibition Control Pain Hypersensitivity via Limiting α2δ-1- and mGluR5-Dependent NMDA Receptor Activity at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- LRRC8A constitutively inhibits pain hypersensitivity in rodent models by restraining NMDA receptor activity at spinal cord synapses.Science translational medicine · 2025Article
- Chloride Homeostasis in Neuronal Disorders: Bridging Measurement to Therapy.Life (Basel, Switzerland) · 2025Review
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Spinal Calcrl+ neurons amplify mechanical itch signaling via synaptic plasticity in chronic itch model.PloS one · 2025Article
- Article
- Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia.Brain : a journal of neurology · 2024Article
- Constitutive KCC2 Cell- and Synapse-Specifically Regulates NMDA Receptor Activity in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy.Frontiers in molecular neuroscience · 2024Review
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
- KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses.Cell reports · 2023Article
- mGluR5 from Primary Sensory Neurons Promotes Opioid-Induced Hyperalgesia and Tolerance by Interacting with and Potentiating Synaptic NMDA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Tiam1 coordinates synaptic structural and functional plasticity underpinning the pathophysiology of neuropathic pain.Neuron · 2023Article
- NMDA Receptors at Primary Afferent-Excitatory Neuron Synapses Differentially Sustain Chemotherapy- and Nerve Trauma-Induced Chronic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- TIAM1-mediated synaptic plasticity underlies comorbid depression-like and ketamine antidepressant-like actions in chronic pain.The Journal of clinical investigation · 2022Article
- HDAC2 in Primary Sensory Neurons Constitutively Restrains Chronic Pain by Repressing α2δ-1 Expression and Associated NMDA Receptor Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic neuropathic pain is a debilitating condition that remains difficult to treat. Diminished synaptic inhibition by GABA and glycine and increased NMDA receptor (NMDAR) activity in the spinal dorsal horn are key mechanisms underlying neuropathic pain. However, the reciprocal relationship between synaptic inhibition and excitation in neuropathic pain is unclear. Here, we show that intrathecal delivery of K(+)-Cl(-) cotransporter-2 (KCC2) using lentiviral vectors produces a complete and long-lasting reversal of pain hypersensitivity induced by nerve injury. KCC2 gene transfer restores Cl(-) homeostasis disrupted by nerve injury in both spinal dorsal horn and primary sensory neurons. Remarkably, restoring Cl(-) homeostasis normalizes both presynaptic and postsynaptic NMDAR activity increased by nerve injury in the spinal dorsal horn. Our findings indicate that nerve injury recruits NMDAR-mediated signaling pathways through the disruption of Cl(-) homeostasis in spinal dorsal horn and primary sensory neurons. Lentiviral vector-mediated KCC2 expression is a promising gene therapy for the treatment of neuropathic pain.
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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.