Affinage

TRPV1

Transient receptor potential cation channel subfamily V member 1 · UniProt Q8NER1

Length
839 aa
Mass
95.0 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPV1 is a polymodal, non-selective cation channel that transduces noxious chemical and physical stimuli into nociceptive signaling and serves as a hub for inflammatory sensitization (PMID:34496225, PMID:31676602). Cryo-EM studies establish that protons, vanilloid agonists, and peptide toxins drive selectivity-filter conformational transitions allosterically coupled to the cytoplasmic gate, and that channel opening proceeds as a sequential trajectory—intracellular gate opening, then selectivity filter dilation, then pore-loop rearrangement (PMID:34496225, PMID:35610228). Capsaicin engages a transmembrane pocket in a 'tail-up, head-down' configuration and stabilizes the open state through 'pull-and-contact' with the S4-S5 linker (PMID:28044278). Beyond exogenous vanilloids, TRPV1 is directly activated by endogenous lipids, including the diacylglycerol metabolites 2-AG and 1-AG generated downstream of phospholipase C, and by retinoids, defining it as an ionotropic receptor for these ligands (PMID:24312564, PMID:23925292). Channel activity is tuned by membrane PIP2, which acts as a direct positive cofactor whose depletion by Ca2+-activated PLCδ underlies capsaicin desensitization (PMID:17074976, PMID:25754030), and by phosphorylation: AKAP150 scaffolds PKA to sensitize the channel (PMID:18381233), PKC phosphorylation at S801 mediates inflammatory sensitization to ligand (PMID:31676602), and PKCε phosphorylation at T704/S502 underlies cytokine sensing in the carotid body (PMID:33180962). Growth-factor signaling sensitizes TRPV1 through PI3K p85β binding to its N-terminus and consequent trafficking to the plasma membrane (PMID:17074976, PMID:15857517). TRPV1 also assembles into heteromeric channels with TRPA1 and TRPV4 that alter its gating and pharmacology (PMID:24643480, PMID:31369032). Beyond its channel role, TRPV1 modulates μ-opioid receptor signaling by binding MOR1 and blocking GRK5- and β-arrestin2-dependent receptor phosphorylation and desensitization (PMID:30940767, PMID:29203659), and in the CNS it localizes to synapses, regulates vesicle recycling, and controls stress responses via a glucocorticoid receptor/HDAC2 pathway (PMID:20483957, PMID:28402861).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2005 Medium

    Established that growth-factor receptor tyrosine kinase signaling sensitizes TRPV1 not only by raising sensitivity but by mobilizing the channel to the plasma membrane, introducing trafficking as a sensitization mechanism.

    Evidence Electrophysiology and subcellular fractionation in DRG neurons and heterologous cells with PI3K/PKC inhibitors (insulin/IGF-I)

    PMID:15857517

    Open questions at the time
    • Direct kinase-channel contacts not mapped
    • Single-lab translocation assay
  2. 2006 High

    Defined a physical mechanism for NGF sensitization by showing PI3K p85β binds the TRPV1 N-terminus to drive surface trafficking, and clarified PIP2 as a direct positive cofactor in excised patches.

    Evidence Yeast two-hybrid, reciprocal Co-IP from HEK293 and DRG neurons, in vitro pulldown, TIRF, and inside-out patch-clamp with direct PIP2/polylysine application

    PMID:17074976

    Open questions at the time
    • Structural basis of p85β-N-terminus binding unresolved
    • How trafficking couples to channel activation not detailed
  3. 2007 Medium

    Showed TRPV1 has cytoskeletal/morphogenic activity beyond ion conduction, with N- and C-terminal domains driving filopodia initiation and microtubule stabilization.

    Evidence Domain-deletion constructs and live imaging in F11, HeLa, and HEK cells

    PMID:17714453

    Open questions at the time
    • Physiological relevance in neurons unclear
    • Mechanism linking channel to myosin upregulation unknown
  4. 2008 High

    Identified AKAP150 as the scaffold that targets PKA to TRPV1, providing a structural basis for kinase-dependent sensitization and inflammatory hyperalgesia.

    Evidence Co-IP from trigeminal neurons, siRNA knockdown, Ca2+ assay in CHO cells, and in vivo AKAP antagonism

    PMID:18381233

    Open questions at the time
    • Phosphosites mediating PKA sensitization not defined here
    • AKAP150 binding interface on TRPV1 unmapped
  5. 2010 Medium

    Extended TRPV1 function to central synapses, showing presence in synaptic vesicles and rapid modulation of vesicle recycling.

    Evidence Synaptosome fractionation, immunocolocalization, and FM4-64 imaging in cortical neurons

    PMID:20483957

    Open questions at the time
    • Endogenous synaptic ligand not identified
    • Single-lab, no genetic confirmation of synaptic role
  6. 2013 High

    Identified endogenous direct activators of TRPV1—PLC-derived monoacylglycerols and retinoids—broadening the channel's ligand repertoire and linking it to lipid signaling and retinoid-induced pain.

    Evidence Inside-out and whole-cell patch-clamp, TRPV1 knockout mice, MAGL inhibition, mass spectrometry; recombinant/native channel activation with retinoids and KO/pharmacology in nociception

    PMID:23925292 PMID:24312564

    Open questions at the time
    • Binding site for monoacylglycerols/retinoids not structurally defined
    • Physiological concentrations driving activation in vivo uncertain
  7. 2013 Medium

    Demonstrated a downstream signaling output of TRPV1 in non-neuronal cells via a TRPV1→p38 MAPK→IL-6 inflammatory axis in corneal fibroblasts.

    Evidence siRNA silencing, Ca2+ imaging, patch-clamp, MAPK phospho-assays, IL-6 ELISA

    PMID:23232207

    Open questions at the time
    • Whether this axis operates in vivo not tested
    • Single-lab cell-line study
  8. 2014 High

    Showed TRPV1 forms defined heteromeric channels with TRPA1, altering stoichiometry, agonist sensitivity, and current magnitude.

    Evidence Concatemers, atomic force microscopy, patch-clamp, epitope mapping

    PMID:24643480

    Open questions at the time
    • Native abundance of TRPV1::TRPA1 heteromers in vivo unclear
    • Structural basis of functional inhibition by TRPA1 not resolved
  9. 2015 Medium

    Consolidated the PIP2/PLCδ feedback model of desensitization, with Ca2+ entry through TRPV1 activating PLCδ to deplete its own positive cofactor PIP2.

    Evidence Excised-patch electrophysiology and PLCδ pharmacology synthesized across labs

    PMID:25754030

    Open questions at the time
    • Quantitative contribution of PIP2 depletion vs other desensitization routes unresolved
  10. 2016 Medium

    Showed that GPCR-evoked PLC signaling activates TRPV1 indirectly through DAG-lipase-generated 2-AG, linking H1 receptor signaling to channel gating.

    Evidence Whole-cell patch-clamp, DAGL/MAGL inhibitors, mass spectrometry in HEK cells co-expressing H1R

    PMID:24312564

    Open questions at the time
    • Single-lab heterologous system
    • Native cell relevance not established here
  11. 2017 Medium

    Defined a non-canonical role for TRPV1 in prolonging opioid analgesia by binding MOR1 and blocking its phosphorylation/desensitization through Ca2+/calmodulin-dependent GRK5 displacement and MAPK-driven nuclear β-arrestin2 sequestration.

    Evidence Co-IP, GRK5 localization and phosphorylation assays, β-arrestin2 translocation, TRPV1 KO mice, CFA inflammatory pain model

    PMID:29203659 PMID:30940767

    Open questions at the time
    • TRPV1-MOR1 binding interface not mapped
    • GRK5 mechanism from single lab without reciprocal structural validation
  12. 2017 Medium

    Linked TRPV1 to central stress regulation through a glucocorticoid receptor/HDAC2 transcriptional pathway, establishing a CNS behavioral output downstream of the channel.

    Evidence Trpv1 KO mice, hippocampal siRNA knockdown, HDAC2 overexpression rescue, behavioral stress assays

    PMID:28402861

    Open questions at the time
    • How channel activity couples to GR/HDAC2 transcription unknown
    • Single-lab study
  13. 2019 High

    Genetically pinned PKC sensitization to a single residue, showing S801 phosphorylation selectively governs ligand (not heat) sensitization and inflammatory pain in vivo.

    Evidence CRISPR S801A knock-in mice, patch-clamp, nocifensive behavior

    PMID:31676602

    Open questions at the time
    • Other PKC sites contributing to sensitization not addressed by this mutation
  14. 2019 Medium

    Demonstrated TRPV1::TRPV4 heteromers in vascular endothelium with a functional role in pathological angiogenesis.

    Evidence Proximity ligation assay, patch-clamp, angiogenesis assays, oxygen-induced retinopathy model

    PMID:31369032

    Open questions at the time
    • Subunit stoichiometry of TRPV1::TRPV4 not resolved
    • Signaling downstream of heteromer in endothelium unclear
  15. 2020 Medium

    Identified PKCε phosphorylation of T704/S502 as the mechanism for carotid-body cytokine sensing, and a GPR18/Gi pathway by which resolvins desensitize TRPV1.

    Evidence Site-directed mutagenesis, patch-clamp, nerve recordings, in vivo allergen challenge; DRG Ca2+ imaging with GPR18 antagonist and pertussis toxin

    PMID:33023902 PMID:33180962

    Open questions at the time
    • How distinct PKC isoforms select sites mechanistically unclear
    • Resolvin/GPR18 effector linking to channel not defined
  16. 2022 High

    Resolved the temporal order of TRPV1 gating, showing activation is a concerted stepwise allosteric process from gate to filter.

    Evidence Cryo-EM thermal-titration ensemble analysis with RTx plus mutagenesis

    PMID:35610228

    Open questions at the time
    • How heat per se drives the same trajectory not directly captured
    • Lipid cofactor states during transitions not modeled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the channel's diverse signaling outputs (synaptic, MOR-modulatory, transcriptional/HDAC2, lipid-deacetylation) are mechanistically coupled to ion conduction versus protein-scaffolding functions remains unresolved.
  • No unified model linking Ca2+ flux to nuclear/transcriptional outputs
  • Binding interfaces for most protein partners unmapped
  • Endogenous activating ligands for central roles unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0008289 lipid binding 4 GO:0060089 molecular transducer activity 3 GO:0140299 molecular sensor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-9709957 Sensory Perception 3 R-HSA-112316 Neuronal System 1
Partners
AKAP150GRK5OPRM1 (MOR1)PIK3R2 (P85Β)TRPA1TRPV4
Complex memberships
TRPV1::TRPA1 heteromeric channelTRPV1::TRPV4 heteromeric channel

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 Cryo-EM structural snapshots of TRPV1 revealed mechanism of polymodal functionality: protons, vanilloid agonists, and peptide toxins induce conformational transitions of the selectivity filter that permit permeation by small and large organic cations, with allosteric coupling identified between sites proximal to the selectivity filter and the cytoplasmic gate. Cryo-electron microscopy (cryo-EM) with multiple ligand conditions Cell High 34496225
2022 Cryo-EM ensemble analysis of TRPV1 with resiniferatoxin (RTx) bound revealed a sequential conformational trajectory: intracellular gate opening occurs first, followed by selectivity filter dilation, then pore loop rearrangement to reach the final open state, demonstrating a concerted stepwise allosteric mechanism. Cryo-EM thermal titration ensemble analysis; site-directed mutagenesis Nature communications High 35610228
2017 Capsaicin binds to a pocket formed by TRPV1 transmembrane segments in a 'tail-up, head-down' configuration, mediated by hydrogen bonds and van der Waals interactions; upon binding, capsaicin stabilizes the open state by 'pull-and-contact' with the S4-S5 linker. Mutagenesis, patch-clamp recording, crystallography, cryo-EM, computational docking, molecular dynamic simulation Protein & cell High 28044278
2006 PI3K p85β subunit physically interacts with the N-terminal region of TRPV1 (demonstrated by yeast 2-hybrid, co-immunoprecipitation from HEK293 cells and DRG neurons, and in vitro pulldown), and this physical coupling facilitates NGF-mediated trafficking of TRPV1 to the plasma membrane, increasing channel number at the surface; wortmannin abolished NGF-mediated sensitization. Yeast two-hybrid, co-immunoprecipitation, in vitro pulldown, TIRF microscopy, electrophysiology, PI3K inhibitor (wortmannin) The Journal of general physiology High 17074976
2008 AKAP150 associates with TRPV1 in trigeminal ganglia neurons and scaffolds PKA to mediate PKA-dependent phosphorylation and sensitization of TRPV1; siRNA knockdown of AKAP150 reduced PKA phosphorylation of TRPV1 and attenuated PKA sensitization of TRPV1 activity; in vivo AKAP antagonist reduced prostaglandin E2-induced thermal hyperalgesia. Co-immunoprecipitation, siRNA knockdown, Ca2+ accumulation assay in CHO cells, in vivo pharmacology Pain High 18381233
2014 TRPV1 and TRPA1 form functional heteromeric channels: TRPV1::TRPA1 concatemers form tetrameric channels (confirmed by AFM) with two TRPV1::TRPA1 units arranged face-to-face; these heteromers respond to TRPV1 agonists (capsaicin, acidic pH, ethanol) but not TRPA1 agonists, have only two capsaicin binding sites, show reduced total current, and TRPA1 presence exerts functional inhibition on TRPV1. Subunit concatemers, atomic force microscopy, electrophysiology, antibody epitope mapping Pflugers Archiv : European journal of physiology High 24643480
2019 PKC-mediated phosphorylation of TRPV1 at S801 contributes to inflammation-mediated sensitization of TRPV1 to ligand (capsaicin) but not to heat in vivo; S801A knock-in mice generated by CRISPR/Cas9 showed impaired PKC-induced sensitization of capsaicin-mediated currents in sensory neurons, attenuated PMA-evoked nocifensive responses, and reduced ongoing inflammatory pain, while basal sensitivity was preserved. CRISPR/Cas9 knock-in mice (S801A), patch-clamp electrophysiology, in vivo behavioral assays The Journal of neuroscience : the official journal of the Society for Neuroscience High 31676602
2013 2-Arachidonoylglycerol (2-AG) and 1-arachidonoylglycerol (1-AG), diacylglycerol metabolites generated by phospholipase C, directly activate TRPV1 on native vascular sensory nerve fibers and in heterologously expressed TRPV1 in whole cells and inside-out membrane patches; monoacylglycerol lipase inhibitors augmented TRPV1-mediated responses to these endogenous ligands, and vasodilator responses to 2-AG were minor in TRPV1 knockout mice. Inside-out patch-clamp, whole-cell recordings, TRPV1 knockout mice, pharmacological inhibition, mass spectrometry (deuterium-labeled substrate metabolism) PloS one High 24312564
2005 Insulin and IGF-I enhance TRPV1-mediated membrane currents through both increased receptor sensitivity and translocation of TRPV1 from cytosol to plasma membrane; this process requires receptor tyrosine kinase activation leading to PI3K and PKC-mediated phosphorylation of TRPV1. Electrophysiology in heterologous expression systems and DRG neurons, subcellular fractionation/translocation assay, pharmacological inhibition of PI3K and PKC Molecular pain Medium 15857517
2017 TRPV1 activation stimulates a MAPK signaling pathway that causes β-arrestin2 to translocate to the nucleus, thereby preventing β-arrestin2 recruitment to the μ-opioid receptor (MOR), blocking MOR internalization and desensitization, and thus prolonging opioid analgesia during inflammation; this mechanism was absent in TRPV1-deficient mice. Cell signaling assays (MAPK, β-arrestin2 nuclear translocation), TRPV1 knockout mice, in vivo CFA inflammatory pain model, pharmacological opioid receptor antagonism Science signaling High 30940767
2017 TRPV1 physically binds MOR1 and blocks opioid-dependent phosphorylation of MOR1 while leaving G protein signaling intact; Ca2+ influx through TRPV1 activates calcium/calmodulin-dependent translocation of GRK5 away from the plasma membrane, thereby blocking its ability to phosphorylate MOR1. Co-immunoprecipitation (TRPV1-MOR1 binding), GRK5 localization assay, Ca2+ influx measurement, phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America Medium 29203659
2017 TRPV1 regulates stress responses through HDAC2: TRPV1-deficient mice show reduced glucocorticoid receptor (GR)-mediated HDAC2 expression and activity; hippocampal knockdown of TRPV1 phenocopied stress resilience, and this behavioral effect was blocked by HDAC2 overexpression, establishing HDAC2 as a molecular link between TRPV1 activity and stress responses. Trpv1 knockout mice, hippocampal siRNA knockdown, HDAC2 overexpression rescue, behavioral stress assays Cell reports Medium 28402861
2007 TRPV1 expression induces filopodia and neurite-like structures; TRPV1 localizes to filopodial tips; the N-terminal intracellular domain of TRPV1 is sufficient for filopodial initiation, while the C-terminal cytoplasmic domain stabilizes microtubules within filopodia; TRPV1 expression also alters cellular distribution and enhances endogenous expression of myosin IIA and myosin IIIA. Live cell microscopy, domain deletion constructs, immunofluorescence in F11, HeLa, and HEK cells Journal of neurochemistry Medium 17714453
2010 TRPV1 is present in synaptic structures (co-localizes with pre- and postsynaptic proteins in cortical neuron spines), is detected in synaptosomes and synaptic transport vesicles, and its activation rapidly modulates vesicle recycling/fusion as demonstrated by FM4-64 dye imaging. Immunofluorescence co-localization, biochemical synaptosome fractionation, FM4-64 vesicle recycling assay, live cell microscopy Journal of cell science Medium 20483957
2013 TRPV1 activation in human corneal fibroblasts (HCF) by capsaicin induces Ca2+ influx, activates MAPK p38 signaling, and leads to IL-6 release; these effects were abolished by TRPV1 siRNA silencing or p38 MAPK inhibitor SB203580, establishing a TRPV1→p38 MAPK→IL-6 pathway in corneal inflammation. siRNA gene silencing, Ca2+ imaging, whole-cell patch-clamp, MAPK phosphorylation assays, IL-6 ELISA Experimental eye research Medium 23232207
2013 Retinoids (naturally occurring and synthetic) directly activate recombinant and native TRPV1 ion channel; in vivo retinoid-induced pain behaviors were eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1, identifying TRPV1 as an ionotropic receptor for retinoids. Electrophysiology with recombinant TRPV1, TRPV1 knockout mice, pharmacological inhibition, in vivo nociceptive behavioral assays The Journal of clinical investigation High 23925292
2020 Resolvins (RvD1, RvD2, RvE1) prevent histamine-induced TRPV1 sensitization in DRG neurons; RvD2 reversal of TRPV1 sensitization is blocked by the GPR18 antagonist O-1918 and by pertussis toxin, establishing a GPR18/Gi-dependent pathway through which RvD2 desensitizes TRPV1. Live Ca2+ imaging of DRG neurons, pharmacological antagonism (GPR18, pertussis toxin), in vivo visceral hypersensitivity models Gut Medium 33023902
2020 PKCε-dependent phosphorylation of TRPV1 at sites T704 and S502 mediates carotid body sensing of asthma-associated Th2 cytokines; site-directed mutagenesis of these residues impaired the response, and systemic PKCε blockade reduced asthmatic bronchoconstriction without affecting oxygen sensing. Site-directed mutagenesis of TRPV1 T704 and S502, patch-clamp, nerve recordings, in situ rat preparations, pharmacological PKCε inhibition, in vivo allergen challenge The Journal of physiology High 33180962
2008 PIP2 directly potentiates TRPV1 in excised inside-out patches; polylysine (a cationic phosphoinositide sequestering agent) inhibited TRPV1 rather than potentiating it, contradicting the proposed tonic inhibition model for PIP2 on TRPV1. Inside-out patch-clamp electrophysiology, direct PIP2 application, polylysine sequestration The Journal of general physiology High 17074976
2016 TRPV1 activation by capsaicin in SUM149PT triple-negative breast cancer cells induced Ca2+ influx (blocked by capsazepine), caused growth inhibition, and induced apoptosis and necrosis, establishing a functional TRPV1-mediated Ca2+-dependent anti-tumor signaling pathway. Ca2+ imaging, pharmacological inhibition (capsazepine), cell viability and apoptosis assays Breast cancer (Dove Medical Press) Low 28008282
2018 Troglitazone activates TRPV1 to cause deacetylation of PPARγ in 3T3-L1 cells; TRPV1 inhibition by capsazepine prevented Troglitazone-induced Ca2+ influx, and inhibition of TRPV1 or Sirtuin 1 prevented PPARγ deacetylation, establishing a TRPV1→Ca2+→Sirtuin1→PPARγ deacetylation pathway. Ca2+ imaging, pharmacological inhibition (capsazepine), TRPV1 overexpression, Western blot for PPARγ acetylation, Sirtuin 1 inhibition Biochimica et biophysica acta. Molecular basis of disease Low 30496795
2019 TRPV1 and TRPV4 form functional heteromeric channel complexes in retinal microvascular endothelial cells (RMECs), demonstrated by proximity ligation assay and electrophysiological recording; pharmacological inhibition of either channel suppressed in vitro tubulogenesis and reduced retinal neovascularization in the oxygen-induced retinopathy mouse model. Proximity ligation assay, patch-clamp electrophysiology, in vitro angiogenesis assays, oxygen-induced retinopathy mouse model Investigative ophthalmology & visual science Medium 31369032
2016 In TRPV1-expressing HEK cells co-expressing the histamine H1 receptor (a PLC-coupled receptor), histamine stimulated 2-arachidonoylglycerol (2-AG) formation via diacylglycerol lipase, and the resulting 2-AG activated TRPV1 currents; this effect was augmented by monoacylglycerol lipase inhibition (JZL184) and abolished by diacylglycerol lipase inhibition, placing 2-AG generation downstream of PLC as a direct TRPV1 activator. Whole-cell patch-clamp, pharmacological enzyme inhibitors, mass spectrometry for 2-AG quantification PloS one Medium 24312564
2015 Ca2+ flowing through TRPV1 activates PLCδ isoforms, resulting in PIP2 depletion that limits TRPV1 channel activity and contributes to capsaicin-induced desensitization; PIP2 acts as a positive cofactor for TRPV1 via direct interaction, and its depletion is a mechanism of desensitization. Excised patch electrophysiology, PIP2 application/depletion experiments, PLCδ pharmacology (reviewed with cited primary data) Pflugers Archiv : European journal of physiology Medium 25754030

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Anandamide and vanilloid TRPV1 receptors. British journal of pharmacology 455 14517174
2005 Structure and function of TRPV1. Pflugers Archiv : European journal of physiology 342 15971082
2012 The functions of TRPA1 and TRPV1: moving away from sensory nerves. British journal of pharmacology 331 22233379
2008 Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology (Bethesda, Md.) 331 19074743
2006 Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. The Journal of general physiology 321 17074976
2017 Understand spiciness: mechanism of TRPV1 channel activation by capsaicin. Protein & cell 260 28044278
2004 Biochemical pharmacology of the vanilloid receptor TRPV1. An update. European journal of biochemistry 235 15128291
2004 The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and pathology. European journal of pharmacology 211 15464045
2019 Inflammation, Cancer and Immunity-Implication of TRPV1 Channel. Frontiers in oncology 207 31681615
2008 Capsaicin (TRPV1 Agonist) therapy for pain relief: farewell or revival? The Clinical journal of pain 189 18209521
2021 Structural snapshots of TRPV1 reveal mechanism of polymodal functionality. Cell 167 34496225
2005 Sensitization and translocation of TRPV1 by insulin and IGF-I. Molecular pain 152 15857517
2008 TRPV1: on the road to pain relief. Current molecular pharmacology 150 20021438
2010 Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology 134 21185837
2006 The TRPV1 receptor and nociception. Seminars in cell & developmental biology 132 17196854
2013 Monoacylglycerols activate TRPV1--a link between phospholipase C and TRPV1. PloS one 131 24312564
2012 Targeting TRPV1 for pain relief: limits, losers and laurels. Expert opinion on investigational drugs 126 22780443
2007 The emerging role of TRPV1 in diabetes and obesity. Trends in pharmacological sciences 125 18055025
2020 TRPV1: Structure, Endogenous Agonists, and Mechanisms. International journal of molecular sciences 119 32408609
2011 TRPV1 and TRPA1 function and modulation are target tissue dependent. The Journal of neuroscience : the official journal of the Society for Neuroscience 116 21775597
2008 A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. Pain 111 18381233
2006 Capsaicin receptor (TRPV1) and non-erosive reflux disease. European journal of gastroenterology & hepatology 109 16462539
2014 Direct evidence for functional TRPV1/TRPA1 heteromers. Pflugers Archiv : European journal of physiology 108 24643480
2012 Multisteric TRPV1 nocisensor: a target for analgesics. Trends in pharmacological sciences 105 23068431
2009 The vanilloid receptor TRPV1: role in cardiovascular and gastrointestinal protection. European journal of pharmacology 95 19879868
2009 Anandamide and the vanilloid receptor (TRPV1). Vitamins and hormones 90 19647120
2016 TRPV1: A Target for Rational Drug Design. Pharmaceuticals (Basel, Switzerland) 86 27563913
2011 A "cute" desensitization of TRPV1. Current pharmaceutical biotechnology 86 20932251
2016 Expression and functionality of TRPV1 in breast cancer cells. Breast cancer (Dove Medical Press) 85 28008282
2006 Expression of transient receptor potential vanilloid 1 (TRPV1) and 2 (TRPV2) in human peripheral blood. Molecular immunology 84 16777226
2011 Regulation of nociceptive transmission at the periphery via TRPA1-TRPV1 interactions. Current pharmaceutical biotechnology 81 20932255
2014 "Hotheaded": the role OF TRPV1 in brain functions. Neuropharmacology 79 24887171
2016 Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 76 27623929
2008 Phospholipase C mediated modulation of TRPV1 channels. Molecular neurobiology 75 18528787
2011 Differential TRPV1 and TRPV2 channel expression in dental pulp. Journal of dental research 74 21406609
2008 TRPV1 receptors in sensitisation of cough and pain reflexes. Pulmonary pharmacology & therapeutics 73 19141328
2008 Role of TRPV1 receptors in descending modulation of pain. Molecular and cellular endocrinology 71 18325659
2015 Phosphoinositide regulation of TRPV1 revisited. Pflugers Archiv : European journal of physiology 70 25754030
2016 Photosensitization in Porphyrias and Photodynamic Therapy Involves TRPA1 and TRPV1. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 27170124
2006 Expression and localization of TRPV1 in human nasal mucosa. Rhinology 65 16792172
2005 Activation and activators of TRPV1 and their pharmaceutical implication. Current pharmaceutical design 64 16101449
2020 Effect of resolvins on sensitisation of TRPV1 and visceral hypersensitivity in IBS. Gut 63 33023902
2011 The role of TRPV1 channel in aged human skin. Journal of dermatological science 63 22154816
2008 TRPV1 receptor in expression of opioid-induced hyperalgesia. The journal of pain 62 18774343
2017 Versatile Roles of Intracellularly Located TRPV1 Channel. Journal of cellular physiology 60 27891582
2013 Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity. The Journal of clinical investigation 60 23925292
2015 Localization and expression of TRPV1 and TRPA1 in the human oropharynx and larynx. Neurogastroenterology and motility 58 26530852
2013 Vanilloid receptor-1 (TRPV1) expression and function in the vasculature of the rat. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 57 24217926
2019 Diverse TRPV1 responses to cannabinoids. Channels (Austin, Tex.) 56 31096838
2015 The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence. Channels (Austin, Tex.) 55 26176938
2011 Complex regulation of TRPV1 and related thermo-TRPs: implications for therapeutic intervention. Advances in experimental medicine and biology 55 21290313
2019 Phosphorylation of TRPV1 S801 Contributes to Modality-Specific Hyperalgesia in Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 31676602
2019 Myrcene and terpene regulation of TRPV1. Channels (Austin, Tex.) 53 31446830
2010 Moving towards supraspinal TRPV1 receptors for chronic pain relief. Molecular pain 53 20937102
2007 TRPV1 expression-dependent initiation and regulation of filopodia. Journal of neurochemistry 53 17714453
2014 TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision. Cells 51 25222270
2017 TRPV1 Regulates Stress Responses through HDAC2. Cell reports 50 28402861
2017 TRPV1 Channels in Immune Cells and Hematological Malignancies. Advances in pharmacology (San Diego, Calif.) 50 28528668
2016 Perspectives of TRPV1 Function on the Neurogenesis and Neural Plasticity. Neural plasticity 50 26881090
2011 TRPV1 function in health and disease. Current pharmaceutical biotechnology 50 20932253
2015 TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch. Neural plasticity 49 26819760
2013 Transient receptor potential vanilloid 1 (TRPV1), TRPV4, and the kidney. Acta physiologica (Oxford, England) 49 23253200
2006 TRPV1 receptors and nasal trigeminal chemesthesis. Chemical senses 49 16908491
2015 Involvement of TRPV1 and TRPA1 in incisional intraoral and extraoral pain. Journal of dental research 48 25576470
2010 TRPV1 splice variants: structure and function. Frontiers in bioscience (Landmark edition) 47 20515731
2021 Interactions between Chemesthesis and Taste: Role of TRPA1 and TRPV1. International journal of molecular sciences 46 33806052
2008 The functional regulation of TRPV1 and its role in pain sensitization. Neurochemical research 46 18528757
2016 Integrating TRPV1 Receptor Function with Capsaicin Psychophysics. Advances in pharmacological sciences 45 26884754
2022 Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis. Nature communications 44 35610228
2010 TRPV1 acts as a synaptic protein and regulates vesicle recycling. Journal of cell science 44 20483957
2015 Interaction between TRPA1 and TRPV1: Synergy on pulmonary sensory nerves. Pulmonary pharmacology & therapeutics 43 26283426
2014 TRPV1 receptor inhibition decreases CCL2-induced hyperalgesia. Neuropharmacology 41 24495396
2012 Functional TRPV1 expression in human corneal fibroblasts. Experimental eye research 41 23232207
2007 Painful toxins acting at TRPV1. Toxicon : official journal of the International Society on Toxinology 41 18061640
2024 Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression. Research (Washington, D.C.) 40 38371274
2007 TRPV1 antagonists as potential antitussive agents. Lung 40 17926096
2019 TRPV1 promotes opioid analgesia during inflammation. Science signaling 37 30940767
2019 Involvement of TRPV1 and TRPV4 Channels in Retinal Angiogenesis. Investigative ophthalmology & visual science 35 31369032
2017 Animal Toxins Providing Insights into TRPV1 Activation Mechanism. Toxins 35 29035314
2017 TRPV1 is a physiological regulator of μ-opioid receptors. Proceedings of the National Academy of Sciences of the United States of America 34 29203659
2015 The involvement of TRPV1 in emesis and anti-emesis. Temperature (Austin, Tex.) 34 27227028
2020 The role of TRPV1 channels in atherosclerosis. Channels (Austin, Tex.) 33 32274960
2019 TRPV1 and TRPV1-Expressing Nociceptors Mediate Orofacial Pain Behaviors in a Mouse Model of Orthodontic Tooth Movement. Frontiers in physiology 33 31620023
2008 Is TRPV1 a useful target in respiratory diseases? Pulmonary pharmacology & therapeutics 33 18992356
2022 TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids. International journal of molecular sciences 32 36077412
2024 TRPV1: The key bridge in neuroimmune interactions. Journal of intensive medicine 30 39310069
2013 The distribution of TRPV1 and TRPV2 in the rat pharynx. Cellular and molecular neurobiology 30 23584686
2012 Expression of TRPV1 in rabbits and consuming hot pepper affects its body weight. Molecular biology reports 30 22327653
2008 Monoacylglycerols activate capsaicin receptor, TRPV1. Lipids 30 18481133
2018 Troglitazone activates TRPV1 and causes deacetylation of PPARγ in 3T3-L1 cells. Biochimica et biophysica acta. Molecular basis of disease 29 30496795
2011 TRPV1 as a cough sensor and its temperature-sensitive properties. Pulmonary pharmacology & therapeutics 29 21215321
2021 TRPV1 in Pain and Itch. Advances in experimental medicine and biology 28 35138618
2020 TRPV1 Channel: A Noxious Signal Transducer That Affects Mitochondrial Function. International journal of molecular sciences 28 33255148
2018 Interaction between TRPV1-expressing neurons in the hypothalamus. Journal of neurophysiology 27 30461371
2022 The interaction of TRPV1 and lipids: Insights into lipid metabolism. Frontiers in physiology 26 36589466
2021 Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression. Frontiers in pharmacology 26 34421611
2020 PKCε stimulation of TRPV1 orchestrates carotid body responses to asthmakines. The Journal of physiology 25 33180962
2016 TRPV1 and TRPM8 in Treatment of Chronic Cough. Pharmaceuticals (Basel, Switzerland) 25 27483288
2016 Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2. Acta physiologica (Oxford, England) 25 28028935
2011 TRPV1 and synaptic transmission. Current pharmaceutical biotechnology 25 20932254

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