ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
Brainstem Pain-Control Circuitry Connectivity in Chronic Neuropathic Pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- Alterations in grey matter density and functional connectivity in trigeminal neuropathic pain and trigeminal neuralgia: A systematic review and meta-analysis.NeuroImage. Clinical · 2019Pooled it
- A meta-analytic study of experimental and chronic orofacial pain excluding headache disorders.NeuroImage. Clinical · 2018Pooled it
- Open-Label Placebo Injection for Chronic Back Pain With Functional Neuroimaging: A Randomized Clinical Trial.JAMA network open · 2024Trial
- Sensory Blurring in Nociplastic Pain: The Role of Descending Inhibitory Dysfunction and Gut-Brain Axis Alterations in Older Adults.Geriatrics (Basel, Switzerland) · 2026Review
- Distribution and subacute modulation of endocannabinoid metabolizing enzymes in the trigeminal complex and midbrain in a pre-clinical model of post-traumatic headache.The journal of headache and pain · 2026Article
- Major depressive disorder is associated with reduced intrinsic connectivity between the bed nucleus of the stria terminalis and ventral striatum.Journal of psychiatry & neuroscience : JPN · 2026Article
- Transcranial Direct Current Stimulation Targeting the Primary Motor Cortex Suppresses Activity in the Ventrolateral Periaqueductal Gray and Alleviates Chronic Pain in a Rat Model of Knee Osteoarthritis.Journal of pain research · 2026Article
- Decoding orofacial pain: a translational review of mechanisms and novel therapies.The journal of headache and pain · 2025Review
- Pain Perception and Modulation: Fundamental Neurobiology and Recent Advances.The European journal of neuroscience · 2025Review
- Microglia in the Rostral Ventromedial Medulla Mediate Synaptic Pruning via the C1q/C3-CR3 Signaling Pathway-A Mechanism for the Chronic Orofacial Pain.Molecular neurobiology · 2025Article
- Aberrant static and dynamic functional connectivity of insular cortex in patients with trigeminal neuralgia.Scientific reports · 2025Article
- When pain is not the same: baroreceptor activation delineates chronic pain and pain-free participants' perception and modulation of noxious pressure.The Journal of physiology · 2025Article
- Alteration of BDNF and noradrenergic markers in locus coeruleus in a mouse model of cancer-induced bone pain.PloS one · 2025Article
- Altered Brain Functional Connectivity and Neurometabolite Correlations in Orofacial Chronic Pain with Central Sensitization.Journal of pain research · 2025Article
- Sex-Specific White Matter Abnormalities Across the Dynamic Pain Connectome in Neuropathic Pain: A Fixel-Based Analysis Study.Human brain mapping · 2025Article
- Expression of Acid-Sensing Ion Channel 3 in Afferents Averts Long-Term Sensitization and the Development of Visceral Pain.International journal of molecular sciences · 2024Article
- The Endogenous Pain Modulatory System as a Healing Mechanism: A Proposal on How to Measure and Modulate It.NeuroSci · 2024Review
- Spared nerve injury leads to reduced activity of neurons projecting from the ventrolateral periaqueductal gray to the locus coeruleus.Molecular brain · 2024Article
- Article
- The 'in's and out's' of descending pain modulation from the rostral ventromedial medulla.Trends in neurosciences · 2024Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preclinical investigations have suggested that altered functioning of brainstem pain-modulation circuits may be crucial for the maintenance of some chronic pain conditions. While some human psychophysical studies show that patients with chronic pain display altered pain-modulation efficacy, it remains unknown whether brainstem pain-modulation circuits are altered in individuals with chronic pain. The aim of the present investigation was to determine whether, in humans, chronic pain following nerve injury is associated with altered ongoing functioning of the brainstem descending modulation systems. Using resting-state functional magnetic resonance imaging, we found that male and female patients with chronic neuropathic orofacial pain show increased functional connectivity between the rostral ventromedial medulla (RVM) and other brainstem pain-modulatory regions, including the ventrolateral periaqueductal gray (vlPAG) and locus ceruleus (LC). We also identified an increase in RVM functional connectivity with the region that receives orofacial nociceptor afferents, the spinal trigeminal nucleus. In addition, the vlPAG and LC displayed increased functional connectivity strengths with higher brain regions, including the hippocampus, nucleus accumbens, and anterior cingulate cortex, in individuals with chronic pain. These data reveal that chronic pain is associated with altered ongoing functioning within the endogenous pain-modulation network. These changes may underlie enhanced descending facilitation of processing at the primary synapse, resulting in increased nociceptive transmission to higher brain centers. Further, our findings show that higher brain regions interact with the brainstem modulation system differently in chronic pain, possibly reflecting top-down engagement of the circuitry alongside altered reward processing in pain conditions.
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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.