ArticleNeuron2017
A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.
Article in Neuron, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 1 of them a synthesis that pooled it.
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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.
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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
189 citing papers in PubMed, 1 synthesis or guideline pooled it, 335 citations in OpenAlex.
- Effects of foot reflexology massage on pregnant women: a systematic review and meta-analysis of randomized controlled studies.Scientific reports · 2024Pooled it
- Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABABritish journal of anaesthesia · 2019Trial
- Targeting Spinal Dorsal Horn Sensitisation in Chronic Pain: Mechanisms and Translational Strategies.Neuroscience bulletin · 2026Review
- The Intraplantar CFA Inflammatory Pain Model Incompletely Captures Pain Comorbidities Across Sexes.Journal of neuroscience research · 2026Article
- Top-down control of the descending pain modulatory system drives multimodal placebo analgesia.Neuron · 2026Article
- Subcutaneous Neuromodulation Activates Central Pain-Suppression Pathways for Analgesia.CNS neuroscience & therapeutics · 2026Article
- Opioid- and NMDA-receptor-dependent neural plasticity mediates long-term analgesia from motor cortical stimulation.bioRxiv : the preprint server for biology · 2026Article
- The ENKCNS neuroscience & therapeutics · 2026Article
- Article
- A Novel Long-range Excitatory Neural Circuit from the Magnocellular Red Nucleus to Spinal Dorsal Horn Facilitates Neuropathic Pain-like Behaviors in Male Mice.Neuroscience bulletin · 2026Article
- Descending inhibitory rostral ventromedial medulla neurons cause widespread antinociception and contribute to the pain-inhibits-pain phenomenon.Nature communications · 2026Article
- Spinal Processing of Spatiotemporally Diverse Tactile Stimuli: Computational Insights into Allodynia and Spinal Cord Stimulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Neuroscientific therapies for subjective tinnitus.Journal of Zhejiang University. Science. B · 2026Review
- Article
- Rostral Ventromedial Medulla (RVM) Projects to the Lateral Hypothalamic Area (LHA) to Drive Aversion and Anxiety.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Targeting sensory nerves in the tumor microenvironment: a new vulnerability in cancer therapy.Cell communication and signaling : CCS · 2026Review
- A GABAergic Projection from the Zona Incerta to the Rostral Ventromedial Medulla Modulates Descending Control of Neuropathic Pain.Brain sciences · 2026Article
- Negative Emotional Influences on Pressure Pain Thresholds: Findings from a Quasi-Randomized Controlled Trial.Journal of pain research · 2026Article
- Morphine Tolerance Gated through EZH2-Mediated Suppression of Trpc5 in Spinal GABAergic Interneurons in Male Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Central neural circuits underlying itch sensation.Nature reviews. Neuroscience · 2025Review
129 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds. Unexpectedly, we found that RVM GABAergic neurons facilitate mechanical pain by inhibiting dorsal horn enkephalinergic/GABAergic interneurons. We further demonstrate that these interneurons gate sensory inputs and control pain through temporally coordinated enkephalin- and GABA-mediated presynaptic inhibition of somatosensory neurons. Our results uncover a descending disynaptic inhibitory circuit that facilitates mechanical pain, is engaged during stress, and could be targeted to establish higher pain thresholds. VIDEO ABSTRACT.
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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.