Antinociceptive effect of the monoterpene R-(+)-limonene in mice

Biol Pharm Bull. 2007 Jul;30(7):1217-20. doi: 10.1248/bpb.30.1217.


In the present study were studied the antinociceptives properties of monoterpene R-(+)-limonene (LM) in chemical and thermal models of nociception in mice. The R-(+)-limonene was administered, intraperitoneally (i.p.), at doses of 25 and 50 mg/kg. The results showed significant inhibition produced on chemical nociception induced by intraperitoneal acetic-acid and in the second phase of subplantar formalin test, but did not manifest a significant effect in hot-plate test. The R-(+)-limonene-induced antinociception in second phase of formalin test was insensitive to naloxone (1 mg/kg, s.c.). It was also demonstrated that R-(+)-limonene (25, 50 mg/kg) neither significantly enhanced the pentobarbital-sleeping time nor impaired the motor performance in rota-rod test, indicating that the observed antinociception is unlikely to be due to sedation or motor abnormality. In conclusion it may be suggested that the R-(+)-limonene presented antinociceptive activity and that, probably, this action can be related with peripheral analgesia, but, not with the stimulation of opioids receptors.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Cyclohexenes / pharmacology*
  • Limonene
  • Male
  • Mice
  • Naloxone / pharmacology
  • Pain Measurement
  • Pentobarbital / pharmacology
  • Stereoisomerism
  • Terpenes / pharmacology*


  • Analgesics
  • Cyclohexenes
  • Terpenes
  • Naloxone
  • Limonene
  • Pentobarbital