Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and antiedematogenic effects in mice.

Authors: Gabriela Trevisan, Mateus F Rossato, Raquel Tonello, Carin Hoffmeister, Jonatas Z Klafke, Fernanda Rosa, Kelly V Pinheiro, Francielle V Pinheiro, Aline A Boligon, Margareth L Athayde, Juliano Ferreira

Journal, date & volume: Naunyn Schmiedebergs Arch. Pharmacol., 2014 Jul , 387, 679-89

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24722818

Abstract
The transient receptor potential ankyrin 1 (TRPA1) has been identified as a relevant target for the development of novel analgesics. Gallic acid (GA) is a polyphenolic compound commonly found in green tea and various berries and possesses a wide range of biological activities. The goal of this study was to identify GA as a TRPA1 antagonist and observe its antinociceptive effects in different pain models. First, we evaluated the ability of GA to affect cinnamaldehyde-induced calcium influx. Then, we observed the antinociceptive and antiedematogenic effects of GA (3-100 mg/kg) oral administration after the intraplantar (i.pl.) injection of TRPA1 agonists (allyl isothiocyanate, cinnamaldehyde, or hydrogen peroxide-H2O2) in either an inflammatory pain model (carrageenan i.pl. injection) or a neuropathic pain model (chronic constriction injury) in male Swiss mice (25-35 g). GA reduced the calcium influx mediated by TRPA1 activation. Moreover, the oral administration of GA decreased the spontaneous nociception triggered by allyl isothiocyanate, cinnamaldehyde, and H2O2. Carrageenan-induced allodynia and edema were largely reduced by the pretreatment with GA. Moreover, the administration of GA was also capable of decreasing cold and mechanical allodynia in a neuropathic pain model. Finally, GA was absorbed after oral administration and did not produce any detectable side effects. In conclusion, we found that GA is a TRPA1 antagonist with antinociceptive properties in relevant models of clinical pain without detectable side effects, which makes it a good candidate for the treatment of painful conditions.