ArticleThe Journal of clinical investigation2007
Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 228 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.
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
228 citing papers in PubMed, 417 citations in OpenAlex.
- Review
- Neurogenic Rosacea and Facial Dysesthesia: Neurovascular-Immune Mechanisms and Translational Therapeutic Perspectives.Medicina (Kaunas, Lithuania) · 2026Review
- Roles of Interleukin-31 in Allergen-Driven Cough: Linking Protease-Activated Receptor-2 Activation and Vagal Ganglion Sensitization in a Dermatophagoides farinae-Induced Asthma Model.Brain and behavior · 2026Article
- Protease-Activated Receptor-2 as a Proteolytic Rheostat in Colorectal and Pancreatic Cancer: From Mechanism to Biomarker-Guided Therapy.International journal of molecular sciences · 2026Review
- Bioactive Constituents and Pharmacological Properties of Lavender Essential Oil: Molecular Mechanisms, Current Evidence, and Future Perspectives.International journal of molecular sciences · 2026Review
- From Inflammation to Neuroplasticity: Molecular Mechanisms of Pain in Acute, Recurrent and Chronic Pancreatitis.International journal of molecular sciences · 2026Review
- Monoclonal antibody inhibition of PAR2 reduces phenotype severity and pain in murine inflammatory bowel disease.Pain reports · 2026Article
- MMP1 and PRSS23 induce PARCommunications biology · 2026Article
- Small peptides derived from the autoinhibitory XY linker of phospholipase C-β isoforms inhibit enzyme activity and reduce inflammation.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- The Mast Cell-PAR2-TRP Axis: A Convergent Mechanism for Visceral Hypersensitivity Independent of Divergent Motility in IBS.Biomolecules · 2026Review
- The exposomal imprint on rosacea: More than skin deep.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026Review
- Modulation of Nociceptive Ion Channels by Protease-Activated Receptor-2 in Inflammatory Pain: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2026Review
- DAB2IP: unifying cardiovascular pathogenesis and cardiovascular brain crosstalk.Frontiers in cardiovascular medicine · 2026Review
- Cellular and molecular changes in the skin driving increased nociception and pain during burn injury and repair.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Research Progress on Upper Airway Cough Syndrome.World journal of otorhinolaryngology - head and neck surgery · 2025Review
- Blockade of PAR2 Signaling by Punicalagin as a Therapeutic Strategy for Atopic Dermatitis.International journal of molecular sciences · 2025Article
- Efficacy of MEDI0618, a pH-dependent monoclonal antibody targeting PAR2, in preclinical models of migraine.Brain : a journal of neurology · 2025Article
- Modulating TRPV1 and TRPA1 channels: a viable strategy for treating asthma using Chinese herbal medicines.Frontiers in pharmacology · 2025Review
- Anesthetic- and Analgesic-Related Drugs Modulating Both Voltage-Gated NaBiomolecules · 2024Review
- Mast cell modulation: A novel therapeutic strategy for abdominal pain in irritable bowel syndrome.Cell reports. Medicine · 2024Review
168 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proinflammatory agents trypsin and mast cell tryptase cleave and activate PAR2, which is expressed on sensory nerves to cause neurogenic inflammation. Transient receptor potential A1 (TRPA1) is an excitatory ion channel on primary sensory nerves of pain pathway. Here, we show that a functional interaction of PAR2 and TRPA1 in dorsal root ganglion (DRG) neurons could contribute to the sensation of inflammatory pain. Frequent colocalization of TRPA1 with PAR2 was found in rat DRG neurons. PAR2 activation increased the TRPA1 currents evoked by its agonists in HEK293 cells transfected with TRPA1, as well as DRG neurons. Application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP(2)) suppressed this potentiation. Decrease of plasma membrane PIP(2) levels through antibody sequestration or PLC-mediated hydrolysis mimicked the potentiating effects of PAR2 activation at the cellular level. Thus, the increased TRPA1 sensitivity may have been due to activation of PLC, which releases the inhibition of TRPA1 from plasma membrane PIP(2). These results identify for the first time to our knowledge a sensitization mechanism of TRPA1 and a novel mechanism through which trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation.
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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.