ArticleeLife2019
Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
- The Wnt5a-PKCδ-GluA1 axis controls synapse-specific plasticity in HIV-1 gp120-induced pain pathogenesis.Brain : a journal of neurology · 2026Article
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Sensory plasticity of dorsal horn silent neurons as a critical mechanism for neuropathic pain.Nature communications · 2026Article
- Spinal Processing of Spatiotemporally Diverse Tactile Stimuli: Computational Insights into Allodynia and Spinal Cord Stimulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- 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
- Automated Neural Dosing for Fast-Acting Subperception Therapy: Sustained Spinal Cord Stimulation Outcomes from a Multicenter Study.Pain and therapy · 2025Article
- Targeting C1q prevents microglia-mediated synaptic removal in neuropathic pain.Nature communications · 2025Article
- The dorsal column nuclei scale mechanical sensitivity in naive and neuropathic pain states.Cell reports · 2025Article
- Model-based analysis of the acute effects of transcutaneous magnetic spinal cord stimulation on micturition after spinal cord injury in humans.PLoS computational biology · 2024Article
- Review
- 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
- Microglial Refinement of A-Fiber Projections in the Postnatal Spinal Cord Dorsal Horn Is Required for Normal Maturation of Dynamic Touch.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Spinal neuromodulation using ultra low frequency waveform inhibits sensory signaling to the thalamus and preferentially reduces aberrant firing of thalamic neurons in a model of neuropathic pain.Frontiers in neuroscience · 2024Article
- Alleviation of neuropathic pain with neuropeptide Y requires spinal Npy1r interneurons that coexpress Grp.JCI insight · 2023Article
- Accelerated brain aging with opioid misuse and HIV: New insights on the role of glially derived pro-inflammation mediators and neuronal chloride homeostasis.Current opinion in neurobiology · 2023Review
- From Low-Grade Inflammation in Osteoarthritis to Neuropsychiatric Sequelae: A Narrative Review.International journal of molecular sciences · 2022Review
- Clinical utilization of fast-acting sub-perception therapy (FAST) in SCS-implanted patients for treatment of mixed pain.Interventional pain medicine · 2022Article
- Targeted ubiquitination of sensory neuron calcium channels reduces the development of neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Excitatory and Inhibitory Neurons of the Spinal Cord Superficial Dorsal Horn Diverge in Their Somatosensory Responses and PlasticityThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Low-Intensity 10 kHz Spinal Cord Stimulation Reduces Behavioral and Neural Hypersensitivity in a Rat Model of Painful Diabetic Neuropathy.Journal of pain research · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Neuropathic pain is a debilitating condition caused by the abnormal processing of somatosensory input. Synaptic inhibition in the spinal dorsal horn plays a key role in that processing. Mechanical allodynia - the misperception of light touch as painful - occurs when inhibition is compromised. Disinhibition is due primarily to chloride dysregulation caused by hypofunction of the potassium-chloride co-transporter KCC2. Here we show, in rats, that excitatory neurons are disproportionately affected. This is not because chloride is differentially dysregulated in excitatory and inhibitory neurons, but, rather, because excitatory neurons rely more heavily on inhibition to counterbalance strong excitation. Receptive fields in both cell types have a center-surround organization but disinhibition unmasks more excitatory input to excitatory neurons. Differences in intrinsic excitability also affect how chloride dysregulation affects spiking. These results deepen understanding of how excitation and inhibition are normally balanced in the spinal dorsal horn, and how their imbalance disrupts somatosensory processing.
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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.