title: The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice.
abstract: OBJECTIVE
  In the present work, we characterize the inflammatory process induced by the topical application of cinnamaldehyde on the skin of mice and verify the participation of transient receptor potential A1 TRPA1 receptors in this process.
  
  
  METHODS
  We measured mouse ear edema and sensitization/desensitization after topical application of cinnamaldehyde or/and capsaicin. We also quantified cellular infiltration through myeloperoxidase (MPO) activity and histological and immunohistochemical analyses and evaluated the expression of TRPV1 and TRPA1 by western blot.
  
  
  RESULTS
  Cinnamaldehyde induced ear edema in mice (1-6μg/ear) with a maximum effect of 4μg/ear. Cinnamaldehyde promoted leukocyte infiltration as detected by increasing MPO activity and confirmed by histological analyses. The edema and cellular infiltration evoked by the application of 4μg/ear of cinnamaldehyde were prevented by topical application of ruthenium red, a non-selective TRP antagonist as well as camphor and HC030031, two TRPA1 receptor antagonists. Cinnamaldehyde-induced edema, but not cellular infiltration, was prevented by topical application of the tachykinin NK1 antagonist, aprepitant, indicating a neuropeptide release phenomenon in this process. Additionally, we observed that repeated topical applications of cinnamaldehyde did not induce changes in sensitization or desensitization with respect to the edema response. Interestingly, repeated treatment with the TRPV1 agonist, capsaicin, abrogated it edematogenic response, confirming the desensitization process and partially decreasing the cinnamaldehyde-induced edema, suggesting the involvement of capsaicin-sensitive fibers.
  
  
  CONCLUSIONS
  Our data demonstrate that the topical application of cinnamaldehyde produces an inflammatory response that is dependent on TRPA1 receptor stimulation.
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas, Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Cássia Regina
authors.initials: CR
authors.lastname: Silva
authors.forename: Sara Marchesan
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Mateus Fortes
authors.initials: MF
authors.lastname: Rossato
authors.forename: Gerusa Duarte
authors.initials: GD
authors.lastname: Dalmolin
authors.forename: Gustavo Petri
authors.initials: GP
authors.lastname: Guerra
authors.forename: Arthur
authors.initials: A
authors.lastname: da Silveira Prudente
authors.forename: Daniela Almeida
authors.initials: DA
authors.lastname: Cabrini
authors.forename: Michel Fleith
authors.initials: MF
authors.lastname: Otuki
authors.forename: Eunice
authors.initials: E
authors.lastname: André
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000287:Administration, Topical; D000818:Animals; D015153:Blotting, Western; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D004487:Edema / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000096:biosynthesis
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D000171:Acrolein; D009195:Peroxidase; D002211:Capsaicin; C012843:cinnamaldehyde