ReviewPain2018
Targeting toll-like receptor-4 (TLR4)-an emerging therapeutic target for persistent pain states.
Review in Pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
83 citing papers in PubMed, 133 citations in OpenAlex.
- Role and mechanism of quercetin via the TLR4/MyD88/IRAK4 signaling pathway in the treatment of allergic rhinitis.Experimental and therapeutic medicine · 2026Article
- IRAK-M attenuates pain hypersensitivity and anxiety-like behaviors in a nitroglycerin-induced chronic migraine mouse model with concomitant reductions in microglial activation and neuroinflammation.The journal of headache and pain · 2026Article
- Presurgical immune biomarkers associated with pain intensity and pain interference recovery after total knee arthroplasty: findings from the PRIME-KNEE study.medRxiv : the preprint server for health sciences · 2026Article
- Sex-specific lateralization of the effects of exogenously-induced neuroimmune activation in the amygdala on pain-like behaviors.Frontiers in pharmacology · 2026Article
- Prenatal alcohol exposure promotes nerve injury-induced pathological pain following morphine treatment via NLRP3-mediated peripheral and central proinflammatory immune actions.Brain, behavior, and immunity · 2025Article
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.Neuropharmacology · 2025Article
- The role of sesamin in alleviating acute and chronic pain: a focus on the TRL4-NF-KB-NLRP3 signaling pathway.Molecular biology reports · 2025Article
- Paclitaxel, interferons and functional reprogramming of tumor-associated macrophages in optimized chemo-immunotherapy.Journal for immunotherapy of cancer · 2025Review
- Inhibition of S100A4 decreases neurotoxic astrocyte reactivity and attenuates neuropathic pain via the TLR4/NF-κB pathway in a rat model of spinal nerve ligation.The journal of headache and pain · 2025Article
- Effect of clove flower extract (Narra J · 2025Article
- Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia.Molecular neurobiology · 2025Review
- Clavulanic acid prevents paclitaxel-induced neuropathic pain through a systemic and central anti-inflammatory effect in mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Article
- Neuroinflammatory and Immunological Aspects of Fibromyalgia.Brain sciences · 2025Review
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.bioRxiv : the preprint server for biology · 2025Article
- The effect of ponicidin on CFA-induced chronic inflammatory pain and its mechanism based on network pharmacology and molecular docking.Frontiers in medicine · 2025Article
- Real-World Effectiveness and Tolerability of Low Dose Naltrexone to Treat Chronic Pain: A Retrospective Cohort Study of One Pain Physician's Practice.Journal of pain research · 2025Article
- Activation of TLR4/CCL2 in Intact Neurons Drives Radicular Injury-Induced Global Nerve Trunk Hypersensitivity in Radiculopathy Preclinical Models.Journal of pain research · 2025Article
- Distinctive salivary oral microbiome in patients with burning mouth syndrome depending on pain intensity compared to healthy subjects.Journal of dental sciences · 2025Article
- TLR4 Targeting: A Promising Therapeutic Approach Across Multiple Human Diseases.Current protein & peptide science · 2025Review
23 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 3 institutions in 1 country.
Funding
Abstract
Toll-like receptors (TLRs) are a family of pattern recognition receptors that initiate signaling in innate and adaptive immune pathways. The highly conserved family of transmembrane proteins comprises an extracellular domain that recognizes exogenous and endogenous danger molecules and an ectodomain that activates downstream pathways in response. Recent studies suggest that continuous activation or dysregulation of TLR signaling may contribute to chronic disease states. The receptor is located not only on inflammatory cells (meningeal and peripheral macrophages) but on neuraxial glia (microglia and astrocytes), Schwann cells, fibroblasts, dorsal root ganglia, and dorsal horn neurons. Procedures blocking TLR functionality have shown pronounced effects on pain behavior otherwise observed in models of chronic inflammation and nerve injury. This review addresses the role of TLR4 as an emerging therapeutic target for the evolution of persistent pain and its role in noncanonical signaling, mediating anomalous pro-algesic actions of opiates. Accordingly, molecules targeting inhibition of this receptor have promise as disease-modifying and opioid-sparing alternatives for persistent pain states.
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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.