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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2014-07, Vol.387 (7), p.679-689
• Main Authors: Trevisan, Gabriela, Rossato, Mateus F., Tonello, Raquel, Hoffmeister, Carin, Klafke, Jonatas Z., Rosa, Fernanda, Pinheiro, Kelly V., Pinheiro, Francielle V., Boligon, Aline A., Athayde, Margareth L., Ferreira, Juliano
• Format: Article
• Language: English
• Subjects: Acrolein - analogs & derivatives; Acrolein - pharmacology; Analgesics - blood; Analgesics - pharmacokinetics; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Anti-Inflammatory Agents - blood; Anti-Inflammatory Agents - pharmacokinetics; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants - pharmacokinetics; Antioxidants - pharmacology; Antioxidants - therapeutic use; Biomedical and Life Sciences; Biomedicine; Edema - drug therapy; Edema - etiology; Edema - metabolism; Gallic Acid - blood; Gallic Acid - pharmacokinetics; Gallic Acid - pharmacology; Gallic Acid - therapeutic use; Hydrogen Peroxide; Hyperalgesia - drug therapy; Hyperalgesia - etiology; Hyperalgesia - metabolism; Male; Mice; Neurosciences; Original Article; Pain - drug therapy; Pain - etiology; Pain - metabolism; Pharmacology/Toxicology; Psychomotor Performance - drug effects; Sciatic Nerve - injuries; Spinal Cord - metabolism; Transient Receptor Potential Channels - agonists; Transient Receptor Potential Channels - antagonists & inhibitors; Transient Receptor Potential Channels - metabolism; TRPA1 Cation Channel
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-014-0978-0

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—H 2 O 2 ) 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 H 2 O 2 . 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.