ArticlePloS one2013
Impaired excitatory drive to spinal GABAergic neurons of neuropathic mice.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Targeting Spinal Dorsal Horn Sensitisation in Chronic Pain: Mechanisms and Translational Strategies.Neuroscience bulletin · 2026Review
- Methylglyoxal alters C-fibre activity-dependent slowing and induces heat hyperalgesia in a sex-dependent manner, in rats.Pain reports · 2026Article
- Structural Plasticity of Peptidergic and Nonpeptidergic C Afferent Terminals in the Medullary Dorsal Horn during Craniofacial Inflammatory Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Alleviation of neuropathic pain with neuropeptide Y requires spinal Npy1r interneurons that coexpress Grp.JCI insight · 2023Article
- CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain.Neuroscience bulletin · 2023Article
- Voltage-gated calcium channel subunit αFrontiers in molecular neuroscience · 2023Article
- Neuropathic pain; what we know and what we should do about it.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- 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
- Spinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy?Channels (Austin, Tex.) · 2021Review
- Glycine Receptors in Spinal Nociceptive Control-An Update.Biomolecules · 2021Review
- Needling Interventions for Sciatica: Choosing Methods Based on Neuropathic Pain Mechanisms-A Scoping Review.Journal of clinical medicine · 2021Article
- Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits.International journal of molecular sciences · 2021Review
- Closing the Critical Period Is Required for the Maturation of Binocular Integration in Mouse Primary Visual Cortex.Frontiers in cellular neuroscience · 2021Article
- Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model.Frontiers in synaptic neuroscience · 2021Article
- Reviewing the case for compromised spinal inhibition in neuropathic pain.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Neonatal Injury Alters Sensory Input and Synaptic Plasticity in GABAergic Interneurons of the Adult Mouse Dorsal Horn.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia.Cell reports · 2019Article
- Nerve injury drives a heightened state of vigilance and neuropathic sensitization inScience advances · 2019Article
- Article
- Developing Modern Pain Therapies.Frontiers in neuroscience · 2019Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Adequate pain sensitivity requires a delicate balance between excitation and inhibition in the dorsal horn of the spinal cord. This balance is severely impaired in neuropathy leading to enhanced pain sensations (hyperalgesia). The underlying mechanisms remain elusive. Here we explored the hypothesis that the excitatory drive to spinal GABAergic neurons might be impaired in neuropathic animals. Transgenic adult mice expressing EGFP under the promoter for GAD67 underwent either chronic constriction injury of the sciatic nerve or sham surgery. In transverse slices from lumbar spinal cord we performed whole-cell patch-clamp recordings from identified GABAergic neurons in lamina II. In neuropathic animals rates of mEPSC were reduced indicating diminished global excitatory input. This downregulation of excitatory drive required a rise in postsynaptic Ca(2+). Neither the density and morphology of dendritic spines on GABAergic neurons nor the number of excitatory synapses contacting GABAergic neurons were affected by neuropathy. In contrast, paired-pulse ratio of Aδ- or C-fiber-evoked monosynaptic EPSCs following dorsal root stimulation was increased in neuropathic animals suggesting reduced neurotransmitter release from primary afferents. Our data indicate that peripheral neuropathy triggers Ca(2+)-dependent signaling pathways in spinal GABAergic neurons. This leads to a global downregulation of the excitatory drive to GABAergic neurons. The downregulation involves a presynaptic mechanism and also applies to the excitation of GABAergic neurons by presumably nociceptive Aδ- and C-fibers. This then leads to an inadequately low recruitment of inhibitory interneurons during nociception. We suggest that this previously unrecognized mechanism of impaired spinal inhibition contributes to hyperalgesia in neuropathy.
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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.