ArticlePain2018
Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.
Article in Pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 28 citations in OpenAlex.
- Doxazosin Alleviates Chronic Orofacial Pain.International journal of molecular sciences · 2026Article
- Locus Coeruleus Noradrenergic-Spinal Projections Contribute to Electroacupuncture-Mediated Antinociception in Postoperative Pain in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Duloxetine deteriorates prefrontal noradrenergic pain facilitation, but reduces locus coeruleus activity to restore endogenous analgesia in chronic neuropathic pain state.Scientific reports · 2025Article
- The differentialFrontiers in pharmacology · 2022Article
- Review
- Migraine in Children Under 7 Years of Age: a Review.Current pain and headache reports · 2020Review
- What goes up must come down: insights from studies on descending controls acting on spinal pain processing.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- A study of cortical and brainstem mechanisms of diffuse noxious inhibitory controls in anaesthetised normal and neuropathic rats.The European journal of neuroscience · 2020Article
- Translational issues in precision medicine in neuropathic pain.Canadian journal of pain = Revue canadienne de la douleur · 2020Review
- Activation of the Intrinsic Pain Inhibitory Circuit from the Midcingulate Cg2 to Zona Incerta Alleviates Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Spinal αBritish journal of pharmacology · 2019Review
- Role of Spinal Cord αFrontiers in neuroscience · 2019Article
- Anti-IL-6 Receptor Antibody Inhibits Spontaneous Pain at the Pre-onset of Experimental Autoimmune Encephalomyelitis in Mice.Frontiers in neurology · 2019Article
- Rescue of Noradrenergic System as a Novel Pharmacological Strategy in the Treatment of Chronic Pain: Focus on Microglia Activation.Frontiers in pharmacology · 2019Review
- Neuropathy following spinal nerve injury shares features with the irritable nociceptor phenotype: A back-translational study of oxcarbazepine.European journal of pain (London, England) · 2019Article
- Modality selective roles of pro-nociceptive spinal 5-HTNeuropharmacology · 2018Article
- The Operant Plantar Thermal Assay: A Novel Device for Assessing Thermal Pain Tolerance in Mice.eNeuroArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve-ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats, these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost, but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. By contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared with sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states, descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.
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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.