ArticleJCI insight2020
The cellular basis of protease-activated receptor 2-evoked mechanical and affective pain.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
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Who cites it
30 citing papers in PubMed, 21 citations in OpenAlex.
- Systematic identification of p11 as a signaling modulator across the GPCRome.Science advances · 2026Article
- 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
- 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
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 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
- Electrophysiological and Proteomic Evidence of Protease-Mediated Pro-nociceptive Signaling in Inflammatory Bowel Disease Patients.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Cellular and molecular changes in the skin driving increased nociception and pain during burn injury and repair.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Synergistic effects of PAR2 and TrkA exacerbate visceral hypersensitivity induced by chronic pancreatitis in rats.IBRO neuroscience reports · 2025Article
- Efficacy of MEDI0618, a pH-dependent monoclonal antibody targeting PAR2, in preclinical models of migraine.Brain : a journal of neurology · 2025Article
- Neuroimmune Circuits in Allergic Diseases.Annual review of immunology · 2025Review
- Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies.Journal of orthopaedic translation · 2024Review
- VLK drives extracellular phosphorylation of EphB2 to govern the EphB2-NMDAR interaction and injury-induced pain.bioRxiv : the preprint server for biology · 2024Article
- SARS-CoV-2 papain-like protease activates nociceptors to drive sneeze and pain.bioRxiv : the preprint server for biology · 2024Article
- Breaking Down the Pain Pathway: Bacterial Proteases Activate Nociceptors to Cause Pain.Cellular and molecular gastroenterology and hepatology · 2024Article
- Update on protease-activated receptor 2 in inflammatory and autoimmune dermatological diseases.Frontiers in immunology · 2024Review
- Targeting sensory neuron GPCRs for peripheral neuropathic pain.Trends in pharmacological sciences · 2023Review
- Protease-Activated Receptor 2 (PAR2) Expressed in Sensory Neurons Contributes to Signs of Pain and Neuropathy in Paclitaxel Treated Mice.The journal of pain · 2023Article
- PAR2 activation in the dura causes acute behavioral responses and priming to glyceryl trinitrate in a mouse migraine model.The journal of headache and pain · 2023Article
- C781, a β-Arrestin Biased Antagonist at Protease-Activated Receptor-2 (PAR2), Displays in vivo Efficacy Against Protease-Induced Pain in Mice.The journal of pain · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Protease-activated receptor 2 (PAR2) has long been implicated in inflammatory and visceral pain, but the cellular basis of PAR2-evoked pain has not been delineated. Although PAR2-evoked pain has been attributed to sensory neuron expression, RNA-sequencing experiments show ambiguous F2rl1 mRNA detection. Moreover, many pharmacological tools for PAR2 are nonspecific, acting also on the Mas-related GPCR family (Mrg) that are highly enriched in sensory neurons. We sought to clarify the cellular basis of PAR2-evoked pain. We developed a PAR2-conditional knockout mouse and specifically deleted PAR2 in all sensory neurons using the PirtCre mouse line. Our behavioral findings show that PAR2 agonist-evoked mechanical hyperalgesia and facial grimacing, but not thermal hyperalgesia, are dependent on PAR2 expression in sensory neurons that project to the hind paw in male and female mice. F2rl1 mRNA is expressed in a discrete population (~4%) of mostly small-diameter sensory neurons that coexpress the Nppb and IL31ra genes. This cell population has been implicated in itch, but our work shows that PAR2 activation in these cells causes clear pain-related behaviors from the skin. Our findings show that a discrete population of DRG sensory neurons mediate PAR2-evoked pain.
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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.