Antinociceptive effect of methyleugenol on formalin-induced hyperalgesia in mice.
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.
Yano
Shingo
S
Central Research Laboratory, Research and Development Division, Tsumura and Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Suzuki
Yasuyuki
Y
Yuzurihara
Mitsutoshi
M
Kase
Yoshio
Y
Takeda
Shuichi
S
Watanabe
Satoshi
S
Aburada
Masaki
M
Miyamoto
Ken-Ichi
K
D000777:Anesthetics / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004008:Diclofenac / Q000627:therapeutic use; D005054:Eugenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005557:Formaldehyde; D018755:GABA Agonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects
D000777:Anesthetics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D004008:Diclofenac; D005557:Formaldehyde; D009118:Muscimol; C005223:methyleugenol; D005054:Eugenol; D016202:N-Methylaspartate; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2