ArticleScience advances2024
Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pharmacological Influences on the R2 Blink Reflex Response in Healthy Participants: A Systematic Review.The European journal of neuroscience · 2026Pooled it
- Top-down control of the descending pain modulatory system drives multimodal placebo analgesia.Neuron · 2026Article
- On the Coexistence of Monitoring and Dampening of Pain Perception During the Fight-or-Flight Response.Cureus · 2026Article
- Review
- The Parafascicular Role in Updating Action from a Spatial to a Visual Strategy Is Driven by Its Glutamatergic Mesencephalic Locomotor Region Inputs.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Spared Nerve Injury Induces Long-Term and Brain Region-Specific Changes in Oligodendrocyte Density in Mice.European journal of pain (London, England) · 2026Article
- Role of Dorsomedial Periaqueductal Gray Glutamatergic Neurons in Promoting Arousal under Multiple General Anesthetics in Mice.Anesthesiology · 2026Article
- Mechanical cues as immunomodulators in neuroinflammation-driven spinal sensitization: analgesic mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Placebo effect on brainstem activity associated with capsaicin-evoked urge to cough in healthy humans.The European respiratory journal · 2026Article
- Neural correlates underlying high-frequency stimulation-induced secondary hyperalgesia in humans.Pain reports · 2025Article
- 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
- Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse Effects and Legal Challenges.Neurology international · 2025Review
- The Locus Coeruleus-Noradrenergic System in the Healthy and Diseased Brain: A Narrative Review.European journal of neurology · 2025Review
- Neuropeptides as transmitters and regulators of the locus coeruleus noradrenergic system.Pharmacological reviews · 2025Review
- Splanchnic and Pelvic Spinal Afferent Pathways Relay Sensory Information From the Mouse Colorectum Into Distinct Brainstem Circuits.Journal of neurochemistry · 2025Article
- A Chemically Stable Photocaged Noradrenaline.ACS chemical neuroscience · 2025Article
- ANA-12 Targets and Inhibits BDNF/TrkB Signaling to Alleviate Pain Behaviors in Rheumatoid Arthritis Mice.Neurochemical research · 2025Article
- Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice.Nature communications · 2025Article
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Abstract
The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. While much previous work has emphasized the role of descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We describe pain-related activity throughout this circuit and report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings substantially revise current models of the DPMS and establish a supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.
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