ArticlePain2016
Toll-like receptor 4 contributes to chronic itch, alloknesis, and spinal astrocyte activation in male mice.
Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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Who cites it
82 citing papers in PubMed, 148 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Sophocarpine alleviates chronic itch in mouse atopic dermatitis by inhibiting spinal astrocyte reactivity and pro-inflammatory signaling.Acta pharmacologica Sinica · 2026Article
- From neuroimmune circuits to targeted therapy of chronic pruritus.Pharmacological reviews · 2026Review
- The neuro-immune insights of itch: peripheral mechanisms and central glial contributions.Cellular & molecular biology letters · 2026Review
- Cross-species transcriptomic evidence for peripheral-central immune crosstalk in atopic dermatitis.Frontiers in immunology · 2026Article
- Spinal and supraspinal mechanisms of chronic itch: from neuronal circuits to the neuro-immune-microbial axis.Frontiers in medicine · 2026Review
- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- Extemporaneous Preparation and Effectiveness of Low-Dose Naltrexone for the Treatment of Uremic Pruritus: A Literature Review and Case Report.Pharmacy (Basel, Switzerland) · 2025Article
- Baicalein ameliorates chronic itch in ACD mice by suppressing the spinal astrocytic STAT3-LCN2 cascade.Acta pharmacologica Sinica · 2025Article
- TLR4 Targeting: A Promising Therapeutic Approach Across Multiple Human Diseases.Current protein & peptide science · 2025Review
- A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch.Science advances · 2024Article
- LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling.Journal of cellular and molecular medicine · 2024Article
- TLR2 Mediates Microglial Activation and Contributes to Central Sensitization in a Recurrent Nitroglycerin-induced Chronic Migraine Model.Molecular neurobiology · 2024Article
- The COL6A5-p.Glu2272* mutation induces chronic itch in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Orexin neurons play contrasting roles in itch and pain neural processing via projecting to the periaqueductal gray.Communications biology · 2024Article
- NLRP3 deficiency aggravated DNFB-induced chronic itch by enhancing type 2 immunity IL-4/TSLP-TRPA1 axis in mice.Frontiers in immunology · 2024Article
- Descending dopaminergic pathway facilitates itch signal processing via activating spinal GRPREMBO reports · 2023Article
- Crisaborole Inhibits Itch and Pain by Preventing Neutrophil Infiltration in a Mouse Model of Atopic Dermatitis.Acta dermato-venereologica · 2023Article
- Article
- An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice.Neuroscience bulletin · 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
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Increasing evidence suggests that Toll-like receptor 4 (TLR4) contributes importantly to spinal cord glial activation and chronic pain sensitization; however, its unique role in acute and chronic itch is unclear. In this study, we investigated the involvement of TLR4 in acute and chronic itch models in male mice using both transgenic and pharmacological approaches. Tlr4 mice exhibited normal acute itch induced by compound 48/80 and chloroquine, but these mice showed substantial reductions in scratching in chronic itch models of dry skin, induced by acetone and diethylether followed by water (AEW), contact dermatitis, and allergic contact dermatitis on the neck. Intrathecal (spinal) inhibition of TLR4 with lipopolysaccharide Rhodobacter sphaeroides did not affect acute itch but suppressed AEW-induced chronic itch. Compound 48/80 and AEW also produced robust alloknesis, a touch-elicited itch in wild-type mice, which was suppressed by intrathecal lipopolysaccharide R sphaeroides and Tlr4 deletion. Acetone and diethylether followed by water induced persistent upregulation of Tlr4 mRNA and increased TLR4 expression in GFAP-expressing astrocytes in spinal cord dorsal horn. Acetone and diethylether followed by water also induced TLR4-dependent astrogliosis (GFAP upregulation) in spinal cord. Intrathecal injection of astroglial inhibitor L-α-aminoadipate reduced AEW-induced chronic itch and alloknesis without affecting acute itch. Spinal TLR4 was also necessary for AEW-induced chronic itch in the cheek model. Interestingly, scratching plays an essential role in spinal astrogliosis because AEW-induced astrogliosis was abrogated by putting Elizabethan collars on the neck to prevent scratching the itchy skin. Our findings suggest that spinal TLR4 signaling is important for spinal astrocyte activation and astrogliosis that may underlie alloknesis and chronic itch.
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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.