ArticlePain2011
Tumor necrosis factor-α induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions.
Article in Pain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
82 citing papers in PubMed, 3 syntheses or guidelines pooled it, 144 citations in OpenAlex.
- Practice advisory for intravenous management of headache disorders in hospitalized patients: a review of the evidence and consensus recommendations.Regional anesthesia and pain medicine · 2026Pooled it
- Imaging the inflammatory phenotype in migraine.The journal of headache and pain · 2022Pooled it
- Association between psoriasis and asthma risk: A meta-analysis.Allergy and asthma proceedings · 2018Pooled it
- Investigation of sumatriptan and ketorolac trometamol in the human experimental model of headache.The journal of headache and pain · 2020Trial
- MRGPRX2 as a novel therapeutic target in headache.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Serum tumor necrosis factor-α levels in migraine: a registry for migraine (REFORM) study.Pain reports · 2026Article
- Meningeal neuropeptide and neuroimmune interactions in the context of migraine.The journal of headache and pain · 2026Review
- The Role of TNF-α in Neuropathic Pain: An Immunotherapeutic Perspective.Life (Basel, Switzerland) · 2025Review
- Meningeal brain borders and migraine headache genesis.Trends in neurosciences · 2024Review
- Neuroimmune interactions in the development and chronification of migraine headache.Trends in neurosciences · 2024Review
- Meningeal Lymphatics in Central Nervous System Diseases.Annual review of neuroscience · 2024Review
- Inhibition of 2-AG hydrolysis alleviates posttraumatic headache attributed to mild traumatic brain injury.The journal of headache and pain · 2024Article
- Inflammatory response of leptomeninges to a single cortical spreading depolarization.The journal of headache and pain · 2024Article
- The glymphatic system in migraine and other headaches.The journal of headache and pain · 2024Review
- Sensitization of meningeal afferents to locomotion-related meningeal deformations in a migraine model.eLife · 2024Article
- Increased Prevalence of Headaches and Migraine in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: Insights from an Italian Cohort Study.Biomedicines · 2024Article
- TRPV1BMC immunology · 2023Article
- Sensitization of meningeal afferents to locomotion-related meningeal deformations in a migraine model.bioRxiv : the preprint server for biology · 2023Article
- Serum tau protein elevation in migraine: a cross-sectional case-control study.The journal of headache and pain · 2023Article
- Meningeal P2X7 Signaling Mediates Migraine-Related Intracranial Mechanical Hypersensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
22 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
The proinflammatory cytokine TNF-α has been shown to promote activation and sensitization of primary afferent nociceptors. The downstream signaling processes that play a role in promoting this neuronal response remain however controversial. Increased TNF-α plasma levels during migraine attacks suggest that local interaction between this cytokine and intracranial meningeal nociceptors plays a role in promoting the headache. Here, using in vivo single unit recording in the trigeminal ganglia of anesthetized rats, we show that meningeal TNF-α action promotes a delayed mechanical sensitization of meningeal nociceptors. Using immunohistochemistry, we provide evidence for non-neuronal localization of the TNF receptors TNFR1 to dural endothelial vascular cells and TNFR2 to dural resident macrophages as well as to some CGRP-expressing dural nerve fibers. We also demonstrate that meningeal vascular TNFR1 is co-localized with COX-1 while the perivascular TNFR2 is co-expressed with COX-2. We further report here for the first time that TNF-α evoked sensitization of meningeal nociceptors is dependent upon local action of cyclooxygenase (COX). Finally, we show that local application of TNF-α to the meninges evokes activation of the p38 MAP kinase in dural blood vessels that also express TNFR1 and that pharmacological blockade of p38 activation inhibits TNF-α evoked sensitization of meningeal nociceptors. Our study suggests that meningeal action of TNF-α could play an important role in the genesis of intracranial throbbing headaches such as migraine through a mechanism that involves at least part activation of non-neuronal TNFR1 and TNFR2 and downstream activation of meningeal non-neuronal COX and the p38 MAP kinase.
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What OpenQuestion holds
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.