ArticleThe Journal of clinical investigation2012
TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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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.
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Who cites it
106 citing papers in PubMed, 166 citations in OpenAlex.
- Mechanisms of pruritus and advances in traditional Chinese medicine therapy (Review).Molecular medicine reports · 2026Review
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Neuro-immune Crosstalk in Atopic Dermatitis: A Multiaxial Regulatory Network and Novel Therapeutic Perspectives.Clinical reviews in allergy & immunology · 2026Review
- The neuro-immune insights of itch: peripheral mechanisms and central glial contributions.Cellular & molecular biology letters · 2026Review
- TRPV1+ neurons promote cutaneous immunity against Schistosoma mansoni.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- HDAC6 inhibition ameliorates sensory hypersensitivity and reduces immune cell signatures in the dorsal root ganglia in murine chronic pain models.Molecular pharmacology · 2025Article
- Article
- Molecular and cellular mechanisms of itch sensation and the anti-itch drug targets.Acta pharmacologica Sinica · 2025Review
- Toll-like receptor 3: a double-edged sword.Biomarker research · 2025Review
- Review
- The Role of Central Sensitization in Autoimmune Connective Tissue Diseases: A Comparative Cross-Sectional Study.International journal of rheumatic diseases · 2025Article
- Targeting exosomal double-stranded RNA-TLR3 signaling pathway attenuates morphine tolerance and hyperalgesia.Cell reports. Medicine · 2024Article
- Nucleic acid sensing in the central nervous system: Implications for neural circuit development, function, and degeneration.Immunological reviews · 2024Review
- Sensory sentinels: Neuroimmune detection and food allergy.Immunological reviews · 2024Review
- Mineralocorticoid Receptor Antagonism Reduces Inflammatory Pain Measures in Mice Independent of the Receptors on Sensory Neurons.Neuroscience · 2024Article
- Role of gut-derived bacterial lipopolysaccharide and peripheral TLR4 in immobilization stress-induced itch aggravation in a mouse model of atopic dermatitis.Scientific reports · 2024Article
- Site-Specific Transient Receptor Potential Channel Mechanisms and Their Characteristics for Targeted Chronic Itch Treatment.Biomolecules · 2024Review
- Pruritogenic Mediators and New Antipruritic Drugs in Atopic Dermatitis.Journal of clinical medicine · 2023Review
- Toll-like receptors: their roles in pathomechanisms of atopic dermatitis.Frontiers in immunology · 2023Review
- An Altered Skin and Gut Microbiota Are Involved in the Modulation of Itch in Atopic Dermatitis.Cells · 2022Review
46 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
13 authors at 4 institutions in 1 country.
Funding
Abstract
Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduced in mice lacking the Tlr3 gene. TLR3 is expressed mainly by small-sized primary sensory neurons in dorsal root ganglions (DRGs) that coexpress the itch signaling pathway components transient receptor potential subtype V1 and gastrin-releasing peptide. Notably, we found that treatment with a TLR3 agonist induces inward currents and action potentials in DRG neurons and elicited scratching in WT mice but not Tlr3(-/-) mice. Furthermore, excitatory synaptic transmission in spinal cord slices and long-term potentiation in the intact spinal cord were impaired in Tlr3(-/-) mice but not Tlr7(-/-) mice. Consequently, central sensitization-driven pain hypersensitivity, but not acute pain, was impaired in Tlr3(-/-) mice. In addition, TLR3 knockdown in DRGs also attenuated pruritus in WT mice. Finally, chronic itch in a dry skin condition was substantially reduced in Tlr3(-/-) mice. Our findings demonstrate a critical role of TLR3 in regulating sensory neuronal excitability, spinal cord synaptic transmission, and central sensitization. TLR3 may serve as a new target for developing anti-itch treatment.
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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.