ArticleBrain : a journal of neurology2022
Distinct brainstem to spinal cord noradrenergic pathways inversely regulate spinal neuronal activity.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Effect of sleep loss on pain-New conceptual and mechanistic avenues.Frontiers in neuroscience · 2022Pooled it
- The Link Between Exposure to Traumatic Stress and Chronic Pain: The Mediation Effect of Hyperarousal Is Moderated by Sensitivity to Pain Traumatization.European journal of pain (London, England) · 2026Article
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- Circuit-selective pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception.Cell reports · 2025Article
- Spared nerve injury induces long-term and brain region-specific changes in oligodendrocyte density in mice.bioRxiv : the preprint server for biology · 2025Article
- A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms.European journal of pain (London, England) · 2025Article
- Pain in Parkinson's disease is impacted by motor complications, anxiety and sleep disturbances.European journal of pain (London, England) · 2025Observational
- Differential Neuronal Activation of Nociceptive Pathways in Neuropathic Pain After Spinal Cord Injury.Cellular and molecular neurobiology · 2025Article
- Diffuse Noxious Inhibitory Controls in Chronic Pain States: Insights from Pre-Clinical Studies.International journal of molecular sciences · 2025Review
- Expression of GAD2 in excitatory neurons projecting from the ventrolateral periaqueductal gray to the locus coeruleus.iScience · 2024Article
- Modulating Neural Circuits of Pain in Preclinical Models: Recent Insights for Future Therapeutics.Cells · 2024Review
- Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation.Science advances · 2024Article
- Opposing Effects on Descending Control of Nociception by µ and κ Opioid Receptors in the Anterior Cingulate Cortex.Anesthesiology · 2024Article
- Understanding of Spinal Wide Dynamic Range Neurons and Their Modulation on Pathological Pain.Journal of pain research · 2024Review
- The noradrenergic subtype of Parkinson disease: from animal models to clinical practice.Nature reviews. Neurology · 2023Review
- A critical brainstem relay for mediation of diffuse noxious inhibitory controls.Brain : a journal of neurology · 2023Article
- Spinal stimulation for motor rehabilitation immediately modulates nociceptive transmission.Journal of neural engineering · 2022Article
- The differentialFrontiers in pharmacology · 2022Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Brainstem to spinal cord noradrenergic pathways include a locus coeruleus origin projection and diffuse noxious inhibitory controls. While both pathways are traditionally viewed as exerting an inhibitory effect on spinal neuronal activity, the locus coeruleus was previously shown to have a facilitatory influence on thermal nocioception according to the subpopulation of coerulean neurons activated. Coupled with knowledge of its functional modular organisation and the fact that diffuse noxious inhibitory controls are not expressed in varied animal models of chronicity, we hypothesized a regulatory role for the locus coeruleus on non-coerulean, discrete noradrenergic cell group(s). We implemented locus coeruleus targeting strategies by microinjecting canine adenovirus encoding for channelrhodopsin-2 under a noradrenaline-specific promoter in the spinal cord (retrogradely labelling a coeruleospinal module) or the locus coeruleus itself (labelling the entire coerulean module). Coeruleospinal module optoactivation abolished diffuse noxious inhibitory controls (two-way ANOVA, P < 0.0001), which were still expressed following locus coeruleus neuronal ablation. We propose that the cerulean system interacts with, but does not directly govern, diffuse noxious inhibitory controls. This mechanism may underlie the role of the locus coeruleus as a 'chronic pain generator'. Pinpointing the functionality of discrete top-down pathways is crucial for understanding sensorimotor modulation in health and disease.
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Registered trials
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