{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:14:21Z","timestamp":1792066461462,"version":"4.4.0"},"reference-count":122,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANR","award":["ANR-21-ASTR-0010"],"award-info":[{"award-number":["ANR-21-ASTR-0010"]}]},{"name":"University of Angers","award":["ANR-21-ASTR-0010"],"award-info":[{"award-number":["ANR-21-ASTR-0010"]}]},{"name":"DGA\/MinDef","award":["ANR-21-ASTR-0010"],"award-info":[{"award-number":["ANR-21-ASTR-0010"]}]},{"name":"INSERM boosting program \u201cChangement Climatique et sant\u00e9\u201d","award":["ANR-21-ASTR-0010"],"award-info":[{"award-number":["ANR-21-ASTR-0010"]}]},{"name":"PHC CEDRE","award":["ANR-21-ASTR-0010"],"award-info":[{"award-number":["ANR-21-ASTR-0010"]}]},{"name":"DGA\/R\u00e9gion Pays de la Loire","award":["ANR-21-ASTR-0010"],"award-info":[{"award-number":["ANR-21-ASTR-0010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Transient Receptor Potential (TRP) channels are ubiquitous proteins involved in a wide range of physiological functions. Some of them are expressed in nociceptors and play a major role in the transduction of painful stimuli of mechanical, thermal, or chemical origin. They have been described in both human and rodent systems. Among them, TRPV1 is a polymodal channel permeable to cations, with a highly conserved sequence throughout species and a homotetrameric structure. It is sensitive to temperature above 43 \u00b0C and to pH below 6 and involved in various functions such as thermoregulation, metabolism, and inflammatory pain. Several TRPV1 mutations have been associated with human channelopathies related to pain sensitivity or thermoregulation. TRPV1 is expressed in a large part of the peripheral and central nervous system, most notably in sensory C and A\u03b4 fibers innervating the skin and internal organs. In this review, we discuss how the transduction of nociceptive messages is activated or impaired by natural compounds and peptides targeting TRPV1. From a pharmacological point of view, capsaicin\u2014the spicy ingredient of chilli pepper\u2014was the first agonist described to activate TRPV1, followed by numerous other natural molecules such as neurotoxins present in plants, microorganisms, and venomous animals. Paralleling their adaptive protective benefit and allowing venomous species to cause acute pain to repel or neutralize opponents, these toxins are very useful for characterizing sensory functions. They also provide crucial tools for understanding TRPV1 functions from a structural and pharmacological point of view as this channel has emerged as a potential therapeutic target in pain management. Therefore, the pharmacological characterization of TRPV1 using natural toxins is of key importance in the field of pain physiology and thermal regulation.<\/jats:p>","DOI":"10.3390\/toxins17020064","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T12:18:56Z","timestamp":1738585136000},"page":"64","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neurotoxins Acting on TRPV1\u2014Building a Molecular Template for the Study of Pain and Thermal Dysfunctions"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2602-7044","authenticated-orcid":false,"given":"Florian","family":"Beignon","sequence":"first","affiliation":[{"name":"University of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaux","family":"Notais","sequence":"additional","affiliation":[{"name":"University of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0128-3167","authenticated-orcid":false,"given":"Sylvie","family":"Diochot","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS U7275, INSERM U1323, IPMC (Institut de Pharmacologie Mol\u00e9culaire et Cellulaire), LabEx ICST (Laboratory of Excellence in Ion Channel Science and Therapeutics), FHU InovPain (F\u00e9d\u00e9ration Hospitalo-Universitaire \u201cInnovative Solutions in Refractory Chronic Pain\u201d), 660 Route des Lucioles, Sophia-Antipolis, F-06560 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-6380","authenticated-orcid":false,"given":"Anne","family":"Baron","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, CNRS U7275, INSERM U1323, IPMC (Institut de Pharmacologie Mol\u00e9culaire et Cellulaire), LabEx ICST (Laboratory of Excellence in Ion Channel Science and Therapeutics), FHU InovPain (F\u00e9d\u00e9ration Hospitalo-Universitaire \u201cInnovative Solutions in Refractory Chronic Pain\u201d), 660 Route des Lucioles, Sophia-Antipolis, F-06560 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-3110","authenticated-orcid":false,"given":"Ziad","family":"Fajloun","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Biotechnology (LBA3B), Department of Cell Culture, Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2881-2962","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Tricoire-Leignel","sequence":"additional","affiliation":[{"name":"University of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Lenaers","sequence":"additional","affiliation":[{"name":"University of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, France"},{"name":"Service de Neurologie, CHU d\u2019Angers, F-49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-2611","authenticated-orcid":false,"given":"C\u00e9sar","family":"Mattei","sequence":"additional","affiliation":[{"name":"University of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The Revised International Association for the Study of Pain Definition of Pain: Concepts, Challenges, and Compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","article-title":"Cellular and Molecular Mechanisms of Pain","volume":"139","author":"Basbaum","year":"2009","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.pop.2012.06.013","article-title":"Pain Processing in the Human Nervous System","volume":"39","author":"Garland","year":"2012","journal-title":"Prim. Care Clin. Off. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s12264-017-0200-8","article-title":"Regulation of Pain and Itch by TRP Channels","volume":"34","author":"Moore","year":"2018","journal-title":"Neurosci. Bull."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jard\u00edn, I., L\u00f3pez, J.J., Diez, R., S\u00e1nchez-Collado, J., Cantonero, C., Albarr\u00e1n, L., Woodard, G.E., Redondo, P.C., Salido, G.M., and Smani, T. (2017). TRPs in Pain Sensation. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00392"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1146\/annurev.physiol.68.040204.101406","article-title":"Permeation and Selectivity of TRP Channels","volume":"68","author":"Owsianik","year":"2006","journal-title":"Annu. Rev. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15435","DOI":"10.1073\/pnas.93.26.15435","article-title":"A Novel Heat-Activated Current in Nociceptive Neurons and Its Sensitization by Bradykinin","volume":"93","author":"Cesare","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.1523\/JNEUROSCI.08-09-03208.1988","article-title":"Capsaicin-Induced Ion Fluxes in Dorsal Root Ganglion Cells in Culture","volume":"8","author":"Wood","year":"1988","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/39807","article-title":"The Capsaicin Receptor: A Heat-Activated Ion Channel in the Pain Pathway","volume":"389","author":"Caterina","year":"1997","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1038\/s41467-018-05339-6","article-title":"The Conformational Wave in Capsaicin Activation of Transient Receptor Potential Vanilloid 1 Ion Channel","volume":"9","author":"Yang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s13238-016-0353-7","article-title":"Understand Spiciness: Mechanism of TRPV1 Channel Activation by Capsaicin","volume":"8","author":"Yang","year":"2017","journal-title":"Protein Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev-cellbio-101011-155833","article-title":"TRP Channels and Pain","volume":"29","author":"Julius","year":"2013","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.mcn.2009.10.006","article-title":"Ablation of TrpV1 Neurons Reveals Their Selective Role in Thermal Pain Sensation","volume":"43","author":"Mishra","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_14","first-page":"E317","article-title":"Heat Activation Is Intrinsic to the Pore Domain of TRPV1","volume":"115","author":"Zhang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1523\/JNEUROSCI.4901-08.2009","article-title":"TRPV1 Is Activated by Both Acidic and Basic pH","volume":"29","author":"Dhaka","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1172\/JCI0215709","article-title":"Amiloride-Blockable Acid-Sensing Ion Channels Are Leading Acid Sensors Expressed in Human Nociceptors","volume":"110","author":"Ugawa","year":"2002","journal-title":"J. Clin. Invest."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10974","DOI":"10.1523\/JNEUROSCI.2619-04.2004","article-title":"Acid-Induced Pain and Its Modulation in Humans","volume":"24","author":"Jones","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1097\/j.pain.0000000000001848","article-title":"TRPV1 Antagonist BCTC Inhibits pH 6.0-Induced Pain in Human Skin","volume":"161","author":"Heber","year":"2020","journal-title":"Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0304-3959(95)00145-X","article-title":"Responses of Adult Human Dorsal Root Ganglion Neurons in Culture to Capsaicin and Low pH","volume":"65","author":"Baumann","year":"1996","journal-title":"Pain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1111\/j.1460-9568.2004.03097.x","article-title":"Background Potassium Channel Block and TRPV1 Activation Contribute to Proton Depolarization of Sensory Neurons from Humans with Neuropathic Pain","volume":"19","author":"Baumann","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1017\/S0033583509990072","article-title":"Structure\u2013Functional Intimacies of Transient Receptor Potential Channels","volume":"42","author":"Latorre","year":"2009","journal-title":"Quart. Rev. Biophys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature12822","article-title":"Structure of the TRPV1 Ion Channel Determined by Electron Cryo-Microscopy","volume":"504","author":"Liao","year":"2013","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20283","DOI":"10.1074\/jbc.M312577200","article-title":"Molecular Determinants of Vanilloid Sensitivity in TRPV1","volume":"279","author":"Gavva","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.toxicon.2012.04.336","article-title":"Receptor-Targeting Mechanisms of Pain-Causing Toxins: How Ow?","volume":"60","author":"Bohlen","year":"2012","journal-title":"Toxicon"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nature12823","article-title":"TRPV1 Structures in Distinct Conformations Reveal Activation Mechanisms","volume":"504","author":"Cao","year":"2013","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature17964","article-title":"TRPV1 Structures in Nanodiscs Reveal Mechanisms of Ligand and Lipid Action","volume":"534","author":"Gao","year":"2016","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1523\/JNEUROSCI.0202-04.2004","article-title":"Identification of a Tetramerization Domain in the C Terminus of the Vanilloid Receptor","volume":"24","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8134","DOI":"10.1073\/pnas.100129497","article-title":"Acid Potentiation of the Capsaicin Receptor Determined by a Key Extracellular Site","volume":"97","author":"Jordt","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12797","DOI":"10.1523\/JNEUROSCI.2324-07.2007","article-title":"Uncoupling Proton Activation of Vanilloid Receptor TRPV1","volume":"27","author":"Ryu","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/emboj.2011.19","article-title":"The Biophysical and Molecular Basis of TRPV1 Proton Gating: Biophysical and Molecular Basis of TRPV1 Proton Gating","volume":"30","author":"Aneiros","year":"2011","journal-title":"EMBO J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.abb.2007.06.035","article-title":"ATP Binding Site on the C-Terminus of the Vanilloid Receptor","volume":"465","author":"Grycova","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.neuron.2007.05.027","article-title":"The Ankyrin Repeats of TRPV1 Bind Multiple Ligands and Modulate Channel Sensitivity","volume":"54","author":"Lishko","year":"2007","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.celrep.2017.10.063","article-title":"Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1","volume":"21","author":"Nersesyan","year":"2017","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/35082088","article-title":"Bradykinin and Nerve Growth Factor Release the Capsaicin Receptor from PtdIns(4,5)P2-Mediated Inhibition","volume":"411","author":"Chuang","year":"2001","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1126\/science.1083646","article-title":"A Modular PIP2 Binding Site as a Determinant of Capsaicin Receptor Sensitivity","volume":"300","author":"Prescott","year":"2003","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13375","DOI":"10.1074\/jbc.C200104200","article-title":"Direct Phosphorylation of Capsaicin Receptor VR1 by Protein Kinase C\u03b5 and Identification of Two Target Serine Residues","volume":"277","author":"Numazaki","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S0896-6273(02)00802-4","article-title":"cAMP-Dependent Protein Kinase Regulates Desensitization of the Capsaicin Receptor (VR1) by Direct Phosphorylation","volume":"35","author":"Bhave","year":"2002","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.pharmthera.2007.01.005","article-title":"Biochemistry and Pharmacology of Endovanilloids","volume":"114","author":"Starowicz","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.neuropharm.2014.05.034","article-title":"\u201cHotheaded\u201d: The Role OF TRPV1 in Brain Functions","volume":"85","author":"Martins","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S0092-8674(02)00637-2","article-title":"Molecular Basis for Species-Specific Sensitivity to \u201cHot\u201d Chili Peppers","volume":"108","author":"Jordt","year":"2002","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107743","DOI":"10.1016\/j.pharmthera.2020.107743","article-title":"Fight Fire with Fire: Neurobiology of Capsaicin-Induced Analgesia for Chronic Pain","volume":"220","author":"Arora","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8924","DOI":"10.1523\/JNEUROSCI.2574-05.2005","article-title":"Camphor Activates and Strongly Desensitizes the Transient Receptor Potential Vanilloid Subtype 1 Channel in a Vanilloid-Independent Mechanism","volume":"25","author":"Xu","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Frias, B., and Merighi, A. (2016). Capsaicin, Nociception and Pain. Molecules, 21.","DOI":"10.3390\/molecules21060797"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cell.2018.06.021","article-title":"Molecular Architecture of the Mouse Nervous System","volume":"174","author":"Zeisel","year":"2018","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1126\/science.288.5464.306","article-title":"Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor","volume":"288","author":"Caterina","year":"2000","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"R885","DOI":"10.1016\/j.cub.2007.08.016","article-title":"Thermoregulation: Channels That Are Cool to the Core","volume":"17","author":"Montell","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1080\/23328940.2015.1048928","article-title":"Effect of Capsaicin on Thermoregulation: An Update with New Aspects","volume":"2","year":"2015","journal-title":"Temperature"},{"key":"ref_48","first-page":"1","article-title":"Autoradiographic Visualization and Pharmacological Characterization of Vanilloid (Capsaicin) Receptors in Several Species, Including Man","volume":"629","author":"Szallasi","year":"1995","journal-title":"Acta Physiol. Scand. Suppl."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"fcac256","DOI":"10.1093\/braincomms\/fcac256","article-title":"Distribution of Acid-Sensing Ion Channel Subunits in Human Sensory Neurons Contrasts with That in Rodents","volume":"4","author":"Shiers","year":"2022","journal-title":"Brain Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1097\/j.pain.0000000000001973","article-title":"Quantitative Differences in Neuronal Subpopulations between Mouse and Human Dorsal Root Ganglia Demonstrated with RNAscope in Situ Hybridization","volume":"161","author":"Shiers","year":"2020","journal-title":"Pain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1097\/j.pain.0000000000001217","article-title":"Comparative Transcriptome Profiling of the Human and Mouse Dorsal Root Ganglia: An RNA-Seq\u2013Based Resource for Pain and Sensory Neuroscience Research","volume":"159","author":"Ray","year":"2018","journal-title":"Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eabj8186","DOI":"10.1126\/scitranslmed.abj8186","article-title":"Spatial Transcriptomics of Dorsal Root Ganglia Identifies Molecular Signatures of Human Nociceptors","volume":"14","author":"Shiers","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1016\/j.celrep.2017.11.066","article-title":"Functional and Molecular Characterization of Mechanoinsensitive \u201cSilent\u201d Nociceptors","volume":"21","author":"Prato","year":"2017","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.1523\/JNEUROSCI.6451-10.2011","article-title":"Trpv1 Reporter Mice Reveal Highly Restricted Brain Distribution and Functional Expression in Arteriolar Smooth Muscle Cells","volume":"31","author":"Cavanaugh","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1476-5381.2012.01851.x","article-title":"The Functions of TRPA1 and TRPV1: Moving Away from Sensory Nerves","volume":"166","author":"Fernandes","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/cr.2011.205","article-title":"TRPV1 Activation Improves Exercise Endurance and Energy Metabolism through PGC-1\u03b1 Upregulation in Mice","volume":"22","author":"Luo","year":"2012","journal-title":"Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.21873\/invivo.11621","article-title":"TRPV1 Mediates Glucose-Induced Insulin Secretion Through Releasing Neuropeptides","volume":"33","author":"Zhong","year":"2019","journal-title":"Vivo"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Panchal, S.K., Bliss, E., and Brown, L. (2018). Capsaicin in Metabolic Syndrome. Nutrients, 10.","DOI":"10.3390\/nu10050630"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"32591","DOI":"10.1074\/jbc.M109.019687","article-title":"The Endoplasmic Reticulum of Dorsal Root Ganglion Neurons Contains Functional TRPV1 Channels","volume":"284","author":"Alonso","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/bja\/aet128","article-title":"Neuroinflammation and the Generation of Neuropathic Pain","volume":"111","author":"Ellis","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.coph.2011.10.022","article-title":"Transient Receptor Potential Vanilloid Type 1 and Pain Development","volume":"12","author":"Palazzo","year":"2012","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0306-4522(98)00012-8","article-title":"A Capsaicin-Receptor Antagonist, Capsazepine, Reduces Inflammation-Induced Hyperalgesic Responses in the Rat: Evidence for an Endogenous Capsaicin-like Substance","volume":"86","author":"Kwak","year":"1998","journal-title":"Neuroscience"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/35012076","article-title":"Vanilloid Receptor-1 Is Essential for Inflammatory Thermal Hyperalgesia","volume":"405","author":"Davis","year":"2000","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1038\/sj.bjp.0705768","article-title":"Activation and Sensitisation of the Vanilloid Receptor: Role in Gastrointestinal Inflammation and Function","volume":"141","author":"Geppetti","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.lfs.2014.10.004","article-title":"A Painful Link between the TRPV1 Channel and Lysophosphatidic Acid","volume":"125","author":"Rosenbaum","year":"2015","journal-title":"Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bujak, J.K., Kosmala, D., Szopa, I.M., Majchrzak, K., and Bednarczyk, P. (2019). Inflammation, Cancer and Immunity\u2014Implication of TRPV1 Channel. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01087"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nrd2280","article-title":"The Vanilloid Receptor TRPV1: 10 Years from Channel Cloning to Antagonist Proof-of-Concept","volume":"6","author":"Szallasi","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e153558","DOI":"10.1172\/JCI153558","article-title":"Nociception and Pain in Humans Lacking a Functional TRPV1 Channel","volume":"133","author":"Katz","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e163735","DOI":"10.1172\/JCI163735","article-title":"A Human TRPV1 Genetic Variant within the Channel Gating Domain Regulates Pain Sensitivity in Rodents","volume":"133","author":"He","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.jsams.2020.04.018","article-title":"Variations in the TRPV1 Gene Are Associated to Exertional Heat Stroke","volume":"23","author":"Bosson","year":"2020","journal-title":"J. Sci. Med. Sport."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/s41436-018-0066-9","article-title":"TRPV1 Variants Impair Intracellular Ca2+ Signaling and May Confer Susceptibility to Malignant Hyperthermia","volume":"21","author":"Lotteau","year":"2019","journal-title":"Genet. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s40265-020-01429-2","article-title":"TRPV1-Targeted Drugs in Development for Human Pain Conditions","volume":"81","author":"Iftinca","year":"2021","journal-title":"Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.toxicon.2013.05.016","article-title":"Different Types of Toxins Targeting TRPV1 in Pain","volume":"71","author":"Min","year":"2013","journal-title":"Toxicon"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/med.21427","article-title":"Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists","volume":"37","author":"Baraldi","year":"2017","journal-title":"Med. Res. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.tips.2008.08.003","article-title":"Body-Temperature Maintenance as the Predominant Function of the Vanilloid Receptor TRPV1","volume":"29","author":"Gavva","year":"2008","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ejphar.2004.07.037","article-title":"The Role of the Vanilloid (Capsaicin) Receptor (TRPV1) in Physiology and Pathology","volume":"500","author":"Nagy","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Carnevale, V., and Rohacs, T. (2016). TRPV1: A Target for Rational Drug Design. Pharmaceuticals, 9.","DOI":"10.3390\/ph9030052"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology Modelling of Protein Structures and Complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1113\/jphysiol.2005.087874","article-title":"Activation of Transient Receptor Potential Vanilloid 1 (TRPV1) by Resiniferatoxin","volume":"567","author":"Raisinghani","year":"2005","journal-title":"J. Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/sj.bjp.0705110","article-title":"Neurogenic Responses Mediated by Vanilloid Receptor-1 (TRPV1) Are Blocked by the High Affinity Antagonist, Iodo-resiniferatoxin","volume":"138","author":"Rigoni","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0306-4522(89)90269-8","article-title":"Resiniferatoxin, a Phorbol-Related Diterpene, Acts as an Ultrapotent Analog of Capsaicin, the Irritant Constituent in Red Pepper","volume":"30","author":"Szallasi","year":"1989","journal-title":"Neuroscience"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1172\/JCI20449","article-title":"Deletion of Vanilloid Receptor 1_expressing Primary Afferent Neurons for Pain Control","volume":"113","author":"Karai","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2786427","DOI":"10.1155\/2017\/2786427","article-title":"Intrathecal Resiniferatoxin Modulates TRPV1 in DRG Neurons and Reduces TNF-Induced Pain-Related Behavior","volume":"2017","author":"Leo","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1021\/bi035981h","article-title":"Resiniferatoxin Binds to the Capsaicin Receptor (TRPV1) near the Extracellular Side of the S4 Transmembrane Domain","volume":"43","author":"Chou","year":"2004","journal-title":"Biochemistry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"E137","DOI":"10.1073\/pnas.1517288113","article-title":"Understanding TRPV1 Activation by Ligands: Insights from the Binding Modes of Capsaicin and Resiniferatoxin","volume":"113","author":"Elokely","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Szallasi, A. (2023). Resiniferatoxin: Nature\u2019s Precision Medicine to Silence TRPV1-Positive Afferents. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015042"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nature05285","article-title":"Spider Toxins Activate the Capsaicin Receptor to Produce Inflammatory Pain","volume":"444","author":"Siemens","year":"2006","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1006\/jmbi.2000.3609","article-title":"Solution Structure of Hanatoxin1, a Gating Modifier of Voltage-Dependent K+ Channels: Common Surface Features of Gating Modifier Toxins","volume":"297","author":"Takahashi","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0041-0101(00)00160-4","article-title":"The Cystine Knot Motif in Toxins and Implications for Drug Design","volume":"39","author":"Craik","year":"2001","journal-title":"Toxicon"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1074\/jbc.M109.054718","article-title":"Target Promiscuity and Heterogeneous Effects of Tarantula Venom Peptides Affecting Na+ and K+ Ion Channels","volume":"285","author":"Redaelli","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/0896-6273(95)90184-1","article-title":"An Inhibitor of the Kv2.1 Potassium Channel Isolated from the Venom of a Chilean Tarantula","volume":"15","author":"Swartz","year":"1995","journal-title":"Neuron"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.cell.2010.03.052","article-title":"A Bivalent Tarantula Toxin Activates the Capsaicin Receptor, TRPV1, by Targeting the Outer Pore Domain","volume":"141","author":"Bohlen","year":"2010","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"25116","DOI":"10.1074\/jbc.M003643200","article-title":"Isolation of a Tarantula Toxin Specific for a Class of Proton-Gated Na+ Channels","volume":"275","author":"Escoubas","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Bae, C., Kalia, J., Song, I., Yu, J., Kim, H.H., Swartz, K.J., and Kim, J.I. (2012). High Yield Production and Refolding of the Double-Knot Toxin, an Activator of TRPV1 Channels. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051516"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e11273","DOI":"10.7554\/eLife.11273","article-title":"Structural Insights into the Mechanism of Activation of the TRPV1 Channel by a Membrane-Bound Tarantula Toxin","volume":"5","author":"Bae","year":"2016","journal-title":"eLife"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"E11837","DOI":"10.1073\/pnas.1809662115","article-title":"TRPV1 Pore Turret Dictates Distinct DkTx and Capsaicin Gating","volume":"115","author":"Geron","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e20210026","DOI":"10.1590\/1678-9199-jvatitd-2021-0026","article-title":"Pain-Related Toxins in Scorpion and Spider Venoms: A Face to Face with Ion Channels","volume":"27","author":"Diochot","year":"2021","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.3390\/toxins7093671","article-title":"Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel","volume":"7","author":"Hakim","year":"2015","journal-title":"Toxins"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e1700810","DOI":"10.1126\/sciadv.1700810","article-title":"A Bimodal Activation Mechanism Underlies Scorpion Toxin\u2013Induced Pain","volume":"3","author":"Yang","year":"2017","journal-title":"Sci. Adv."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"8297","DOI":"10.1038\/ncomms9297","article-title":"A Pain-Inducing Centipede Toxin Targets the Heat Activation Machinery of Nociceptor TRPV1","volume":"6","author":"Yang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.toxicon.2020.02.016","article-title":"A Centipede Toxin Causes Rapid Desensitization of Nociceptor TRPV1 Ion Channel","volume":"178","author":"Zhu","year":"2020","journal-title":"Toxicon"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Chen, B., Hu, Z., Chen, X., and Zeng, X. (2024). Molecular Mechanisms of Two Novel and Selective TRPV1 Channel Activators. Int. J. Biol. Macromol., 275.","DOI":"10.1016\/j.ijbiomac.2024.133658"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.bbagen.2017.01.004","article-title":"Protein Toxins of the Echis Coloratus Viper Venom Directly Activate TRPV1","volume":"1861","author":"Geron","year":"2017","journal-title":"Biochim. Et. Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-ento-120709-144844","article-title":"Urticating Hairs in Arthropods: Their Nature and Medical Significance","volume":"56","author":"Battisti","year":"2011","journal-title":"Annu. Rev. Entomol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Yao, Z., Kamau, P.M., Han, Y., Hu, J., Luo, A., Luo, L., Zheng, J., Tian, Y., and Lai, R. (2019). The Latoia Consocia Caterpillar Induces Pain by Targeting Nociceptive Ion Channel TRPV1. Toxins, 11.","DOI":"10.3390\/toxins11120695"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Gewehr, C., Oliveira, S.M., Rossato, M.F., Trevisan, G., Dalmolin, G.D., Rigo, F.K., De Castro J\u00fanior, C.J., Cordeiro, M.N., Ferreira, J., and Gomez, M.V. (2013). Mechanisms Involved in the Nociception Triggered by the Venom of the Armed Spider Phoneutria Nigriventer. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002198"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"15544","DOI":"10.1021\/bi051494l","article-title":"An Inhibitor of TRPV1 Channels Isolated from Funnel Web Spider Venom","volume":"44","author":"Kitaguchi","year":"2005","journal-title":"Biochemistry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"107826","DOI":"10.1016\/j.neuropharm.2019.107826","article-title":"Phoneutria Toxin PnTx3-5 Inhibits TRPV1 Channel with Antinociceptive Action in an Orofacial Pain Model","volume":"162","author":"Souza","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Nikolaev, M.V., Dorofeeva, N.A., Komarova, M.S., Korolkova, Y.V., Andreev, Y.A., Mosharova, I.V., Grishin, E.V., Tikhonov, D.B., and Kozlov, S.A. (2017). TRPV1 Activation Power Can Switch an Action Mode for Its Polypeptide Ligands. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177077"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Monastyrnaya, M., Peigneur, S., Zelepuga, E., Sintsova, O., Gladkikh, I., Leychenko, E., Isaeva, M., Tytgat, J., and Kozlovskaya, E. (2016). Kunitz-Type Peptide HCRG21 from the Sea Anemone Heteractis Crispa Is a Full Antagonist of the TRPV1 Receptor. Mar. Drugs, 14.","DOI":"10.3390\/md14120229"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Elnahriry, K.A., Wai, D.C.C., Ashwood, L.M., Naseem, M.U., Szanto, T.G., Guo, S., Panyi, G., Prentis, P.J., and Norton, R.S. (2024). Structural and Functional Characterisation of Tst2, a Novel TRPV1 Inhibitory Peptide from the Australian Sea Anemone Telmatactis Stephensoni. Biochim. Et. Biophys. Acta (BBA) Proteins Proteom., 1872.","DOI":"10.1016\/j.bbapap.2023.140952"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0306-4522(92)90465-E","article-title":"A Highly Potent and Selective Receptor Antagonist from the Venom of the Agelenopsis Aperta Spider","volume":"51","author":"Kiskin","year":"1992","journal-title":"Neuroscience"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s00424-016-1801-1","article-title":"Antinociceptive Effect of a Novel Armed Spider Peptide Tx3-5 in Pathological Pain Models in Mice","volume":"468","author":"Oliveira","year":"2016","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"23914","DOI":"10.1074\/jbc.M800776200","article-title":"Analgesic Compound from Sea Anemone Heteractis Crispa Is the First Polypeptide Inhibitor of Vanilloid Receptor 1 (TRPV1)","volume":"283","author":"Andreev","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1134\/S106816201202015X","article-title":"Interaction of Sea Anemone Heteractis Crispa Kunitz Type Polypeptides with Pain Vanilloid Receptor TRPV1: In Silico Investigation","volume":"38","author":"Zelepuga","year":"2012","journal-title":"Russ. J. Bioorg Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"5100","DOI":"10.3390\/md11125100","article-title":"Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia","volume":"11","author":"Andreev","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Sintsova, O., Gladkikh, I., Klimovich, A., Palikova, Y., Palikov, V., Styshova, O., Monastyrnaya, M., Dyachenko, I., Kozlov, S., and Leychenko, E. (2021). TRPV1 Blocker HCRG21 Suppresses TNF-\u03b1 Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070716"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Peigneur, S., Paiva, A.L.B., Cordeiro, M.N., Borges, M.H., Diniz, M.R.V., De Lima, M.E., and Tytgat, J. (2018). Phoneutria Nigriventer Spider Toxin PnTx2-1 (\u03b4-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating. Toxins, 10.","DOI":"10.3390\/toxins10090337"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/S0140-6736(10)60354-6","article-title":"Ziconotide for Treatment of Severe Chronic Pain","volume":"375","author":"Schmidtko","year":"2010","journal-title":"Lancet"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"107474","DOI":"10.1016\/j.pharmthera.2020.107474","article-title":"Hyperthermia Induced by Transient Receptor Potential Vanilloid-1 (TRPV1) Antagonists in Human Clinical Trials: Insights from Mathematical Modeling and Meta-Analysis","volume":"208","author":"Garami","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e80139","DOI":"10.7554\/eLife.80139","article-title":"TRPV1 Drugs Alter Core Body Temperature via Central Projections of Primary Afferent Sensory Neurons","volume":"11","author":"Yue","year":"2022","journal-title":"eLife"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Logashina, Y.A., Palikova, Y.A., Palikov, V.A., Kazakov, V.A., Smolskaya, S.V., Dyachenko, I.A., Tarasova, N.V., and Andreev, Y.A. (2021). Anti-Inflammatory and Analgesic Effects of TRPV1 Polypeptide Modulator APHC3 in Models of Osteo- and Rheumatoid Arthritis. Mar. Drugs, 19.","DOI":"10.3390\/md19010039"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/2\/64\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:13Z","timestamp":1760027113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/2\/64"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":122,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["toxins17020064"],"URL":"https:\/\/doi.org\/10.3390\/toxins17020064","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}