ArticleThe Journal of clinical investigation2023
A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 21 citations in OpenAlex.
- TRPV1‑mediated central sensitisation: Core mechanisms of migraine chronification and novel targeted therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Aging-Related Changes in the Injury Response of the Peripheral Nervous System.Neuroscience bulletin · 2026Review
- Identification of a human mitochondrial isoform of TRPV1: a thermostat regulating mitochondrial maximal temperature?Cellular and molecular life sciences : CMLS · 2026Article
- TRPV1 antagonism occurs through diverse structural mechanisms.bioRxiv : the preprint server for biology · 2026Article
- Mechanism of capsaicin entry into buried vanilloid sites in TRPV1.Nature chemical biology · 2025Article
- ROS-scavenging hydrogen nanotherapy simultaneously targets inflammation and pain in rheumatoid arthritis.Materials today. Bio · 2025Article
- Review
- The Role of Biomarkers in Acute Pain: A Narrative Review.Pain and therapy · 2025Review
- Neurotoxins Acting on TRPV1-Building a Molecular Template for the Study of Pain and Thermal Dysfunctions.Toxins · 2025Review
- Neurotoxins Acting on TRPV1-Building a Molecular Template for the Study of Pain and Thermal Dysfunctions.Toxins · 2025Review
- Advancing Pain Understanding and Drug Discovery: Insights from Preclinical Models and Recent Research Findings.Pharmaceuticals (Basel, Switzerland) · 2024Review
- PIK3CA mutations enhance the adipogenesis of ADSCs in facial infiltrating lipomatosis through TRPV1.iScience · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- TRPV1 Channels in the Central Nervous System as Drug Targets.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Lysophosphatidic acid contributes to myocardial ischemia/reperfusion injury by activating TRPV1 in spinal cord.Basic research in cardiology · 2024Article
- Resiniferatoxin: Nature's Precision Medicine to Silence TRPV1-Positive Afferents.International journal of molecular sciences · 2023Review
- Striving toward hyperthermia-free analgesia: lessons from loss-of-function mutations of human TRPV1.The Journal of clinical investigation · 2023Article
- A journey from molecule to physiology andFrontiers in pharmacology · 2023Review
- The role of TRPV1 in RA pathogenesis: worthy of attention.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
Abstract
Pain signals are relayed to the brain via a nociceptive system, and in rare cases, this nociceptive system contains genetic variants that can limit the pain response. Here, we questioned whether a human transient receptor potential vanilloid 1 (TRPV1) missense variant causes a resistance to noxious stimuli and, further, whether we could target this region with a cell-permeable peptide as a pain therapeutic. Initially using a computational approach, we identified a human K710N TRPV1 missense variant in an otherwise highly conserved region of mammalian TRPV1. After generating a TRPV1K710N-knockin mouse using CRISPR/Cas9, we discovered that the K710N variant reduced capsaicin-induced calcium influx in dorsal root ganglion neurons. The TRPV1K710N rodents also had less acute behavioral responses to noxious chemical stimuli and less hypersensitivity to nerve injury, while their response to noxious heat remained intact. Furthermore, blocking this K710 region in WT rodents using a cell-penetrating peptide limited acute behavioral responses to noxious stimuli and returned pain hypersensitivity induced by nerve injury to baseline levels. These findings identify K710 TRPV1 as a discrete site that is crucial for the control of nociception and provide insights into how to leverage rare genetic variants in humans to uncover fresh strategies for developing pain therapeutics.
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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.