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.
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Abbreviations
- AITC:
-
Allyl isothiocyanate
- CCI:
-
Chronic constriction injury
- DPPH:
-
2,2-Diphenyl-1-picrylhydrazyl
- GA:
-
Gallic acid
- H2O2 :
-
Hydrogen peroxide
- 4-HNE:
-
4-Hydroxynonenal
- i.p.:
-
Intraperitoneal
- PWT:
-
Paw withdrawal threshold
- PBS:
-
Phosphate-buffered saline
- p.o.:
-
Oral route
- s.c.:
-
Subcutaneously
- TRPA1:
-
Transient receptor potential ankyrin 1
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Fellowships from Conselho Nacional de Desenvolvimento Científico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) (Brazil) supported this work.
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Trevisan, G., Rossato, M.F., Tonello, R. et al. Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and antiedematogenic effects in mice. Naunyn-Schmiedeberg's Arch Pharmacol 387, 679–689 (2014). https://doi.org/10.1007/s00210-014-0978-0
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DOI: https://doi.org/10.1007/s00210-014-0978-0