ArticleeLife2014
Criticality and degeneracy in injury-induced changes in primary afferent excitability and the implications for neuropathic pain.
Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 60 citations in OpenAlex.
- Nociceptors use multiple neurotransmitters to drive pain.bioRxiv : the preprint server for biology · 2025Article
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- Intrinsic neural diversity quenches the dynamic volatility of neural networks.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair.Communications biology · 2023Review
- Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity in Human Sensory Neuron Somata Parallel Alterations Described in Spontaneously Active Rodent Nociceptors.The journal of pain · 2022Article
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- A functional subdivision within the somatosensory system and its implications for pain research.Neuron · 2022Review
- A population ofF1000Research · 2022Article
- Ion-channel degeneracy: Multiple ion channels heterogeneously regulate intrinsic physiology of rat hippocampal granule cells.Physiological reports · 2021Article
- Effects of Several Classes of Voltage-Gated Ion Channel Conductances on Gamma and Theta Oscillations in a Hippocampal Microcircuit Model.Frontiers in computational neuroscience · 2021Article
- Computational analysis of a 9D model for a small DRG neuron.Journal of computational neuroscience · 2020Article
- Circuit Stability to Perturbations Reveals Hidden Variability in the Balance of Intrinsic and Synaptic Conductances.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Intermittent Failure of Spike Propagation in Primary Afferent Neurons during Tactile Stimulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Article
- Using dynamic clamp to quantify pathological changes in the excitability of primary somatosensory neurons.The Journal of physiology · 2018Article
- Using an engineered glutamate-gated chloride channel to silence sensory neurons and treat neuropathic pain at the source.Brain : a journal of neurology · 2017Article
- Combined Changes in Chloride Regulation and Neuronal Excitability Enable Primary Afferent Depolarization to Elicit Spiking without Compromising its Inhibitory Effects.PLoS computational biology · 2016Article
- Enhanced excitability and suppression of A-type K(+) currents in joint sensory neurons in a murine model of antigen-induced arthritis.Scientific reports · 2016Article
- A Probabilistic Model for Estimating the Depth and Threshold Temperature of C-fiber Nociceptors.Scientific reports · 2015Article
- Ion channel degeneracy enables robust and tunable neuronal firing rates.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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4 authors at 2 institutions in 2 countries.
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Abstract
Neuropathic pain remains notoriously difficult to treat despite numerous drug targets. Here, we offer a novel explanation for this intractability. Computer simulations predicted that qualitative changes in primary afferent excitability linked to neuropathic pain arise through a switch in spike initiation dynamics when molecular pathologies reach a tipping point (criticality), and that this tipping point can be reached via several different molecular pathologies (degeneracy). We experimentally tested these predictions by pharmacologically blocking native conductances and/or electrophysiologically inserting virtual conductances. Multiple different manipulations successfully reproduced or reversed neuropathic changes in primary afferents from naïve or nerve-injured rats, respectively, thus confirming the predicted criticality and its degenerate basis. Degeneracy means that several different molecular pathologies are individually sufficient to cause hyperexcitability, and because several such pathologies co-occur after nerve injury, that no single pathology is uniquely necessary. Consequently, single-target-drugs can be circumvented by maladaptive plasticity in any one of several ion channels. DOI: http://dx.doi.org/10.7554/eLife.02370.001.
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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.