Antinociceptive effect of methyleugenol on formalin-induced hyperalgesia in mice

Eur J Pharmacol. 2006 Dec 28;553(1-3):99-103. doi: 10.1016/j.ejphar.2006.09.020. Epub 2006 Sep 23.


The effects of methyleugenol, an essential oil isolated from Asiasari radix, on antinociception were examined using the formalin test in mice. Oral administration of 10 mg/kg methyleugenol significantly decreased the duration of licking and biting behavior in the second phase without affecting that of the first phase, as did diclofenac, a non-steroidal anti-inflammatory drug. Methyleugenol also inhibited pain-related behaviors induced by intrathecal injection of N-methyl-d-aspartic acid (NMDA), while diclofenac did not affect these behaviors. These effects of methyleugenol were suppressed by bicuculline, a gamma-aminobutyric acid(A) (GABA(A)) antagonist. Muscimol, a GABA(A) agonist, displays the same action as methyleugenol with respect to the formalin test and NMDA-induced behaviors. Methyleugenol did not affect cyclooxygenase-1 and -2 activities. These results suggest that the antinociceptive effect of methyleugenol on the second phase of formalin-induced pain may be due to the inhibition of NMDA receptor-mediated hyperalgesia via GABA(A) receptors.

MeSH terms

  • Anesthetics / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Behavior, Animal / drug effects
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Diclofenac / therapeutic use
  • Eugenol / analogs & derivatives*
  • Eugenol / therapeutic use
  • Excitatory Amino Acid Agonists / pharmacology
  • Formaldehyde*
  • GABA Agonists / pharmacology
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / drug therapy*
  • Male
  • Mice
  • Muscimol / pharmacology
  • N-Methylaspartate / pharmacology
  • Nociceptors / drug effects


  • Anesthetics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Excitatory Amino Acid Agonists
  • GABA Agonists
  • Diclofenac
  • Formaldehyde
  • Muscimol
  • methyleugenol
  • Eugenol
  • N-Methylaspartate
  • Cyclooxygenase 1
  • Cyclooxygenase 2