Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal Dysfunctions
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...
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2025-01-01
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| author | Florian Beignon Margaux Notais Sylvie Diochot Anne Baron Ziad Fajloun Hélène Tricoire-Leignel Guy Lenaers César Mattei |
| author_facet | Florian Beignon Margaux Notais Sylvie Diochot Anne Baron Ziad Fajloun Hélène Tricoire-Leignel Guy Lenaers César Mattei |
| author_sort | Florian Beignon |
| collection | DOAJ |
| description | 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 °C and to pH below 6 and involved in various functions such as thermoregulation, metabolism, and inflammatory pain. Several <i>TRPV1</i> 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 Aδ 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—the spicy ingredient of chilli pepper—was 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. |
| format | Article |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-ff4f8490d5a041cd87815a6324bddd162025-08-20T02:04:05ZengMDPI AGToxins2072-66512025-01-011726410.3390/toxins17020064Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal DysfunctionsFlorian Beignon0Margaux Notais1Sylvie Diochot2Anne Baron3Ziad Fajloun4Hélène Tricoire-Leignel5Guy Lenaers6César Mattei7University of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, FranceUniversity of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, FranceUniversité Côte d’Azur, CNRS U7275, INSERM U1323, IPMC (Institut de Pharmacologie Moléculaire et Cellulaire), LabEx ICST (Laboratory of Excellence in Ion Channel Science and Therapeutics), FHU InovPain (Fédération Hospitalo-Universitaire “Innovative Solutions in Refractory Chronic Pain”), 660 Route des Lucioles, Sophia-Antipolis, F-06560 Nice, FranceUniversité Côte d’Azur, CNRS U7275, INSERM U1323, IPMC (Institut de Pharmacologie Moléculaire et Cellulaire), LabEx ICST (Laboratory of Excellence in Ion Channel Science and Therapeutics), FHU InovPain (Fédération Hospitalo-Universitaire “Innovative Solutions in Refractory Chronic Pain”), 660 Route des Lucioles, Sophia-Antipolis, F-06560 Nice, FranceLaboratory of Applied Biotechnology (LBA3B), Department of Cell Culture, Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, LebanonUniversity of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, FranceUniversity of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, FranceUniversity of Angers, INSERM U1083, CNRS UMR6015, MITOVASC, SFR ICAT, F-49000 Angers, FranceTransient 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 °C and to pH below 6 and involved in various functions such as thermoregulation, metabolism, and inflammatory pain. Several <i>TRPV1</i> 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 Aδ 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—the spicy ingredient of chilli pepper—was 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.https://www.mdpi.com/2072-6651/17/2/64TRPV1painthermoregulationtoxinsvenomsagonists |
| spellingShingle | Florian Beignon Margaux Notais Sylvie Diochot Anne Baron Ziad Fajloun Hélène Tricoire-Leignel Guy Lenaers César Mattei Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal Dysfunctions Toxins TRPV1 pain thermoregulation toxins venoms agonists |
| title | Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal Dysfunctions |
| title_full | Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal Dysfunctions |
| title_fullStr | Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal Dysfunctions |
| title_full_unstemmed | Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal Dysfunctions |
| title_short | Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal Dysfunctions |
| title_sort | neurotoxins acting on trpv1 building a molecular template for the study of pain and thermal dysfunctions |
| topic | TRPV1 pain thermoregulation toxins venoms agonists |
| url | https://www.mdpi.com/2072-6651/17/2/64 |
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