title: The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil.
abstract: Mustard oil (MO) is a plant-derived irritant that has been extensively used in experimental models to induce pain and inflammation. The noxious effects of MO are currently ascribed to specific activation of the cation channel TRPA1 in nociceptive neurons. In contrast to this view, we show here that the capsaicin receptor TRPV1 has a surprisingly large contribution to aversive and pain responses and visceral irritation induced by MO. Furthermore, we found that this can be explained by previously unknown properties of this compound. First, MO has a bimodal effect on TRPA1, producing current inhibition at millimolar concentrations. Second, it directly and stably activates mouse and human recombinant TRPV1, as well as TRPV1 channels in mouse sensory neurons. Finally, physiological temperatures enhance MO-induced TRPV1 stimulation. Our results refute the dogma that TRPA1 is the sole nocisensor for MO and motivate a revision of the putative roles of these channels in models of MO-induced pain and inflammation. We propose that TRPV1 has a generalized role in the detection of irritant botanical defensive traits and in the coevolution of multiple mammalian and plant species.
authors.affiliation: Laboratory for Ion Channel Research, Department of Molecular Cell Biology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Everaerts
authors.forename: Maarten
authors.initials: M
authors.lastname: Gees
authors.forename: Yeranddy A
authors.initials: YA
authors.lastname: Alpizar
authors.forename: Ricard
authors.initials: R
authors.lastname: Farre
authors.forename: Cindy
authors.initials: C
authors.lastname: Leten
authors.forename: Aurelia
authors.initials: A
authors.lastname: Apetrei
authors.forename: Ilse
authors.initials: I
authors.lastname: Dewachter
authors.forename: Fred
authors.initials: F
authors.lastname: van Leuven
authors.forename: Rudi
authors.initials: R
authors.lastname: Vennekens
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ridder
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Thomas
authors.initials: T
authors.lastname: Voets
authors.forename: Karel
authors.initials: K
authors.lastname: Talavera
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003556:Cystitis / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009149:Mustard Plant / Q000633:toxicity*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D010938:Plant Oils / Q000633:toxicity*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D010938:Plant Oils; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D015740:Calcitonin Gene-Related Peptide; C027793:mustard oil