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

Naunyn Schmiedebergs Arch Pharmacol. 2014 Jul;387(7):679-89. doi: 10.1007/s00210-014-0978-0. Epub 2014 Apr 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • 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
  • Pain / drug therapy
  • Pain / etiology
  • Pain / metabolism
  • Psychomotor Performance / drug effects
  • Sciatic Nerve / injuries
  • Spinal Cord / metabolism
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / agonists
  • Transient Receptor Potential Channels / antagonists & inhibitors*
  • Transient Receptor Potential Channels / metabolism

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Antioxidants
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • Gallic Acid
  • Acrolein
  • Hydrogen Peroxide
  • cinnamaldehyde