Evidence map›Paper›PMID 35523367›Full record

ArticleNeuroImage2022

Tonic pain alters functional connectivity of the descending pain modulatory network involving amygdala, periaqueductal gray, parabrachial nucleus and anterior cingulate cortex.

Timothy J Meeker, Anne-Christine Schmid, Michael L Keaser, Shariq A Khan, Rao P Gullapalli, Susan G Dorsey, Joel D Greenspan, David A Seminowicz

Abstract read
In one paragraph

Article in NeuroImage, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. A review of descending pain modulation in humans.Frontiers in pain research (Lausanne, Switzerland) · 2026
    Review
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  5. Article
  6. Review
  7. Article
  8. Review
  9. Methanol Extract ofMolecules (Basel, Switzerland) · 2024
    Article
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  12. Melatonin Induces Analgesic Effects through MTResearch (Washington, D.C.) · 2024
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Pain in the claustrum.Neurobiology of pain (Cambridge, Mass.)
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Timothy J MeekerDepartment of Neurosurgery, Johns Hopkins University, Baltimore, MD 21287, United States; Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, United States; Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, MD 21201, United States. Electronic address: tmeeker3@jhmi.edu.
Anne-Christine SchmidDepartment of Neurosurgery, Johns Hopkins University, Baltimore, MD 21287, United States; Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, United States; Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, MD 21201, United States; Clinical Neuroengineering, BrainMind Institute and Centre of Neuroprosthetics (CNP), Swiss Federal Institute of Technology (EPFL) Geneva, Switzerland and Swiss Federal Institute of Technology Valais (EPFL Valais), Sion, Switzerland; WyssCenter of Bio- and Neuroengineering, Geneva, Switzerland.
Michael L KeaserDepartment of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, United States; Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, MD 21201, United States.
Shariq A KhanDepartment of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, United States.
Rao P GullapalliDepartment of Diagnostic Radiology and Nuclear Imaging, University of Maryland School of Medicine, Baltimore MD, 21201, United States.
Susan G DorseyCenter to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, MD 21201, United States; Department of Pain and Translational Symptom Sciences, University of Maryland School of Nursing, Baltimore, MD 21201, United States.
Joel D GreenspanDepartment of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, United States; Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, MD 21201, United States.
David A SeminowiczDepartment of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, United States; Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, MD 21201, United States.

Funding

Translational Phenotyping CoreP30NR014129 · NINR · UNIVERSITY OF MARYLAND BALTIMORE · PI GREENSPAN, JOEL D. · 2012 to 2016
$2.3M
NINR NIH HHS P30 NR014129
6 · The paper itself

Abstract

introductionResting state functional connectivity (FC) is widely used to assess functional brain alterations in patients with chronic pain. However, reports of FC accompanying tonic pain in pain-free persons are rare. A network we term the Descending Pain Modulatory Network (DPMN) is implicated in healthy and pathologic pain modulation. Here, we evaluate the effect of tonic pain on FC of specific nodes of this network: anterior cingulate cortex (ACC), amygdala (AMYG), periaqueductal gray (PAG), and parabrachial nuclei (PBN).

methodsIn 50 pain-free participants (30F), we induced tonic pain using a capsaicin-heat pain model. functional MRI measured resting BOLD signal during pain-free rest with a 32 °C thermode and then tonic pain where participants experienced a previously warm temperature combined with capsaicin. We evaluated FC from ACC, AMYG, PAG, and PBN with correlation of self-report pain intensity during both states. We hypothesized tonic pain would diminish FC dyads within the DPMN.

resultsOf all hypothesized FC dyads, only PAG and subgenual ACC was weakly altered during pain (F = 3.34; p = 0.074; pain-free>pain d = 0.25). After pain induction sACC-PAG FC became positively correlated with pain intensity (R = 0.38; t = 2.81; p = 0.007). Right PBN-PAG FC during pain-free rest positively correlated with subsequently experienced pain (R = 0.44; t = 3.43; p = 0.001). During pain, this connection's FC was diminished (paired t=-3.17; p = 0.0026). In whole-brain analyses, during pain-free rest, FC between left AMYG and right superior parietal lobule and caudate nucleus were positively correlated with subsequent pain. During pain, FC between left AMYG and right inferior temporal gyrus negatively correlated with pain. Subsequent pain positively correlated with right AMYG FC with right claustrum; right primary visual cortex and right temporo-occipitoparietal junction

conclusionWe demonstrate sACC-PAG tonic pain FC positively correlates with experienced pain and resting right PBN-PAG FC correlates with subsequent pain and is diminished during tonic pain. Finally, we reveal PAG- and right AMYG-anchored networks which correlate with subsequently experienced pain intensity. Our findings suggest specific connectivity patterns within the DPMN at rest are associated with subsequently experienced pain and modulated by tonic pain. These nodes and their functional modulation may reveal new therapeutic targets for neuromodulation or biomarkers to guide interventions.

Indexed as

Chronic PainParabrachial NucleusAmygdalaBrain MappingCapsaicinGyrus CinguliHumansMagnetic Resonance ImagingPeriaqueductal GrayCapsaicinCapsaicin-heat pain modelCentral sensitizationDescending pain modulatory networkParabrachial nucleiPeriaqueductal graySeed-driven functional connectivity

Identifiers

PMID35523367
PMCPMC9250649

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.