ArticleMolecular pain
Association of TRPV1 and TLR4 through the TIR domain potentiates TRPV1 activity by blocking activation-induced desensitization.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Identification of potential microRNAs and KEGG pathways in denervation muscle atrophy based on meta-analysis.Scientific reports · 2021Pooled it
- Molecular mechanisms and therapeutic perspectives in vulvodynia: From current evidence to future investigations.Cell reports. Medicine · 2026Review
- Bidirectional crosstalk between TRP channels and Toll-like receptors in inflammation and host defense.Journal of neuroinflammation · 2026Review
- Enhanced TRPV1 activation through TLR-4 and PKA signaling in Dorsal Root Ganglia Neurons.bioRxiv : the preprint server for biology · 2026Article
- A neuroimmune axis linking S100A8/9 to itch sensitization in both bullous pemphigoid and atopic dermatitis.JID innovations : skin science from molecules to population health · 2026Article
- Nociceptor neurons shape antiviral immunity.Journal of neuroinflammation · 2026Review
- Neural Circuits between Nodose Ganglion and Pulmonary Neuroendocrine Cells Regulate Lung Inflammatory Responses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRPV1+ neurons promote cutaneous immunity against Schistosoma mansoni.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Role of microbiota in pain: From bench to bedside.iMetaOmics · 2025Review
- Article
- Cannabidiol Alleviates Chronic Prostatitis and Chronic Pelvic Pain SyndromeThe world journal of men's health · 2025Article
- The influence of sex on neuroimmune communication, pain, and physiology.Biology of sex differences · 2024Review
- Lipopolysaccharide pretreatment increases the sensitivity of the TRPV1 channel and promotes an anti-inflammatory phenotype of capsaicin-activated macrophages.Journal of inflammation (London, England) · 2024Article
- Neuroimmune recognition and regulation in the respiratory system.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Induction of antiviral interferon-stimulated genes by neuronal STING promotes the resolution of pain in mice.The Journal of clinical investigation · 2024Article
- TRPV1 Is a Potential Tumor Suppressor for Its Negative Association with Tumor Proliferation and Positive Association with Antitumor Immune Responses in Pan-Cancer.Journal of oncology · 2022Article
- Implications of Transient Receptor Potential Cation Channels in Migraine Pathophysiology.Neuroscience bulletin · 2021Review
- How Do Sensory Neurons Sense Danger Signals?Trends in neurosciences · 2020Review
- TRPA1 and TRPV1 channels participate in atmospheric-pressure plasma-induced [CaScientific reports · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe have previously reported that histamine-induced pruritus was attenuated in toll-like receptor 4 (TLR4) knockout mice due to decreased transient receptor potential V1 (TRPV1) sensitivity. Our results implied that TLR4 potentiated TRPV1 activation in sensory neurons; however, the molecular mechanism has yet to be elucidated. In this study, we investigated the molecular mechanisms of TLR4-mediated TRPV1 potentiation using TLR4-deficient sensory neurons and a heterologous expression system.
methodsPrimary sensory neurons were obtained from wild-type or TLR4 knockout mice, and HEK293T cells expressing TRPV1 and TLR4 were prepared by transient transfection. TRPV1 activity was analyzed by calcium imaging, fluorophotometry, and patch-clamp recording. Subcellular protein distribution was tested by immunocytochemistry and cell surface biotinylation assay. Protein interaction was assessed by western blot and immunoprecipitation assay.
resultsDirect association between TRPV1 and TLR4 was detected in HEK293T cells upon heterologous TRPV1 and TLR4 expression. In an immunoprecipitation assay using TLR4-deletion mutants and soluble toll/interleukin-1 receptor (TIR) protein, the cytoplasmic TIR domain of TLR4 was required for TLR4-TRPV1 association and TRPV1 potentiation. In TLR4-deficient sensory neurons, the activation-induced desensitization of TRPV1 increased, accompanied by enhanced TRPV1 clearance from the cell membrane upon activation compared to wild-type neurons. In addition, heterologous TLR4 expression inhibited activation-induced TRPV1 endocytosis and lysosomal degradation in HEK293T cells.
conclusionOur data show that direct association between TRPV1 and TLR4 through the TIR domain enhances TRPV1 activity by blocking activation-induced TRPV1 desensitization.
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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.