ArticlePain2016
Targeted overexpression of tumor necrosis factor-α increases cyclin-dependent kinase 5 activity and TRPV1-dependent Ca2+ influx in trigeminal neurons.
Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled 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.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Trigeminal neuralgia and genetics: A systematic review.Molecular painPooled it
- Short-Term Changes in Persistent Ocular Discomfort After Add-On Motugivatrep in Patients with Dry Eye Disease: A Retrospective Observational Study.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- Cdk5 modulates orofacial pain through P2X2/3 purinergic receptor-mediated signaling in trigeminal neurons.Frontiers in pharmacology · 2026Article
- TRPC4 Mediates Trigeminal Neuropathic Pain via CaCNS neuroscience & therapeutics · 2025Article
- Transient receptor potential vanilloid 1 inhibition reduces brain damage by suppressing neuronal apoptosis after intracerebral hemorrhage.Brain pathology (Zurich, Switzerland) · 2024Article
- Sex differences in PD-L1-induced analgesia in paclitaxel-induced peripheral neuropathy mice depend on TRPV1-based inhibition of CGRP.CNS neuroscience & therapeutics · 2024Article
- PACAP38/mast-cell-specific receptor axis mediates repetitive stress-induced headache in mice.The journal of headache and pain · 2024Article
- Mast-cell-specific receptor mediates alcohol-withdrawal-associated headache in male mice.Neuron · 2024Article
- Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain.Frontiers in pain research (Lausanne, Switzerland) · 2024Review
- The role of TRPV1 in RA pathogenesis: worthy of attention.Frontiers in immunology · 2023Review
- Neuronally expressed PDL1, not PD1, suppresses acute nociception.Brain, behavior, and immunity · 2022Article
- Stellate Ganglia and Cardiac Sympathetic Overactivation in Heart Failure.International journal of molecular sciences · 2022Review
- TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner.Scientific reports · 2022Article
- Cdk5 regulates IP3R1-mediated CaCellular and molecular life sciences : CMLS · 2022Article
- Oral cancer induced TRPV1 sensitization is mediated by PARScientific reports · 2022Article
- TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal CellsFrontiers in pharmacology · 2022Article
- Post-inflammatory Abdominal Pain in Patients with Inflammatory Bowel Disease During Remission: A Comprehensive Review.Crohn's & colitis 360 · 2021Review
- Protocols for Characterization of Cdk5 Kinase Activity.Current protocols · 2021Article
- TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice.Neuroscience bulletin · 2021Article
- Chemokines and Pain in the Trigeminal System.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
We reported earlier that TNF-α, a proinflammatory cytokine implicated in many inflammatory disorders causing orofacial pain, increases the activity of Cdk5, a key kinase involved in brain development and function and recently found to be involved in pain signaling. To investigate a potential mechanism underlying inflammatory pain in trigeminal ganglia (TGs), we engineered a transgenic mouse model (TNF) that can conditionally overexpresses TNF-α upon genomic recombination by Cre recombinase. TNF mice were bred with Nav1.8-Cre mouse line that expresses the Cre recombinase in sensory neurons to obtain TNF-α:Nav1.8-Cre (TNF-α cTg) mice. Although TNF-α cTg mice appeared normal without any gross phenotype, they displayed a significant increase in TNF-α levels after activation of NFκB signaling in the TG. IL-6 and MCP-1 levels were also increased along with intense immunostaining for Iba1 and GFAP in TG, indicating the presence of infiltrating macrophages and the activation of satellite glial cells. TNF-α cTg mice displayed increased trigeminal Cdk5 activity, and this increase was associated with elevated levels of phospho-T407-TRPV1 and capsaicin-evocated Ca influx in cultured trigeminal neurons. Remarkably, this effect was prevented by roscovitine, an inhibitor of Cdk5, which suggests that TNF-α overexpression induced sensitization of the TRPV1 channel. Furthermore, TNF-α cTg mice displayed more aversive behavior to noxious thermal stimulation (45°C) of the face in an operant pain assessment device as compared with control mice. In summary, TNF-α overexpression in the sensory neurons of TNF-α cTg mice results in inflammatory sensitization and increased Cdk5 activity; therefore, this mouse model would be valuable for investigating the mechanism of TNF-α involved in orofacial pain.
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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.