ArticleNeuron2023
A cholinergic circuit that relieves pain despite opioid tolerance.
Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07394647 (Transcutaneous Auricular Vagus Nerve Stimulation for Preventing Emergence Agitation and Delirium After Pediatric Tonsillectomy and Adenoidectomy), which is not on this map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Transcutaneous Auricular Vagus Nerve Stimulation for Preventing Emergence Agitation and Delirium After Pediatric Tonsillectomy and Adenoidectomy: A Randomized, Double-Blind, Interventional Study
Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Spinal cord stimulation: An emerging strategy for chronic pain relief after spinal cord injury.Neural regeneration research · 2026Article
- The subthalamic nucleus-ventral pallidum projection targeting cholinergic circuits modulates chronic pain.PLoS biology · 2026Article
- In Vivo Imaging of Neuronal Activity Shifts in the Somatosensory Cortex After Morphine Tolerance in Mice.Addiction biology · 2026Article
- A molecularly defined basalo-prefrontal-thalamic circuit regulates sensory and affective dimensions of pain in male mice.Nature communications · 2026Article
- Nicotinic acetylcholine receptors in pain modulation.Frontiers in pharmacology · 2026Review
- Pain Perception and Modulation: Fundamental Neurobiology and Recent Advances.The European journal of neuroscience · 2025Review
- Cholinergic neuronal activity promotes diffuse midline glioma growth through muscarinic signaling.Cell · 2025Article
- Phospho-CREB Regulation on NMDA Glutamate Receptor 2B and Mitochondrial Calcium Uniporter in the Ventrolateral Periaqueductal Gray Controls Chronic Morphine Withdrawal in Male Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Discovery of Novel Pain Regulators Through Integration of Cross-Species High-Throughput Data.CNS neuroscience & therapeutics · 2025Article
- Convergent state-control of endogenous opioid analgesia.bioRxiv : the preprint server for biology · 2025Article
- Acetylcholine in the hippocampus: problems and achievements.Frontiers in neural circuits · 2025Review
- Angelica gigas Nakai (Korean Dang-gui) Root Alcoholic Extracts in Health Promotion and Disease Therapy - active Phytochemicals and In Vivo Molecular Targets.Pharmaceutical research · 2025Article
- Hypoperfusion of periaqueductal gray as an imaging biomarker in chronic migraine beyond diagnosis: A 3D pseudocontinuous arterial spin labeling MR imaging.Brain and behavior · 2024Article
- Mapping of afferent and efferent connections of phenylethanolamine N-methyltransferase-expressing neurons in the nucleus tractus solitarii.CNS neuroscience & therapeutics · 2024Article
- Activation of Pedunculopontine Tegmental Nucleus Alleviates the Pain Induced by the Lesion of Midbrain Dopaminergic Neurons.International journal of molecular sciences · 2024Article
- Santacruzamate A Alleviates Pain and Pain-Related Adverse Emotions through the Inhibition of Microglial Activation in the Anterior Cingulate Cortex.ACS pharmacology & translational science · 2024Article
- Neurokinin1 - cholinergic receptor mechanisms in the medial Septum-Dorsal hippocampus axis mediates experimental neuropathic pain.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Chronic pain is a tremendous burden for afflicted individuals and society. Although opioids effectively relieve pain, significant adverse outcomes limit their utility and efficacy. To investigate alternate pain control mechanisms, we explored cholinergic signaling in the ventrolateral periaqueductal gray (vlPAG), a critical nexus for descending pain modulation. Biosensor assays revealed that pain states decreased acetylcholine release in vlPAG. Activation of cholinergic projections from the pedunculopontine tegmentum to vlPAG relieved pain, even in opioid-tolerant conditions, through ⍺7 nicotinic acetylcholine receptors (nAChRs). Activating ⍺7 nAChRs with agonists or stimulating endogenous acetylcholine inhibited vlPAG neuronal activity through Ca
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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.