The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice

Aims: 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. Main 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. Key findings: Cinnamaldehyde induced ear edema in mice (1-6 mu g/ear) with a maximum effect of 4 mu g/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 4 mu g/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. Significance: Our data demonstrate that the topical application of cinnamaldehyde produces an inflammatory response that is dependent on TRPA1 receptor stimulation. (C) 2011 Published by Elsevier Inc.