Effects of (-)-linalool in the acute hyperalgesia induced by carrageenan, L-glutamate and prostaglandin E2

Eur J Pharmacol. 2004 Aug 30;497(3):279-84. doi: 10.1016/j.ejphar.2004.06.006.


A series of studies performed in our laboratory have shown that (-)-linalool, the natural occurring enantiomer in essential oils, possesses anti-inflammatory and antinociceptive effects in different animal models. The antinociceptive effect of (-)-linalool has been ascribed to the stimulation of the cholinergic, opioidergic and dopaminergic systems, to its local anesthetic activity and to the blockade of N-methyl-D-aspartate (NMDA) receptors. In this study, we investigated the effect of systemic administration of (-)-linalool in the paw withdrawal test in rats, a model of thermal hyperalgesia induced by monolateral subplantar injection of carrageenan, L-glutamate or prostaglandin E(2). Carrageenan and L-glutamate induced a hyperalgesic effect on the injection side. In contrast, prostaglandin E(2) induced hyperalgesia in both the injection side and the contralateral side. Pretreatment with (-)-linalool (50-150 mg/kg) inhibited the development of acute hyperalgesia induced by carrageenan in the injected paw, with no effect on the contralateral paw. Furthermore, (-)-linalool at the highest dose used (200 mg/kg), reduced and reverted the decrease in paw withdrawal latencies induced by L-glutamate on the ipsilateral side, showing antihyperalgesic and antinociceptive effects. An antinociceptive effect was apparent also in the contralateral paw. Finally, (-)-linalool (200 mg/kg) increased paw withdrawal latency on the side contralateral to prostaglandin E(2) injection, but not on the side of the injection. The efficacy of (-)-linalool in decreasing the hyperalgesia induced by carrageenan, L-glutamate and prostaglandin E(2) suggests that this compound might be useful in pain conditions sustained by the development of neuronal sensitization.

MeSH terms

  • Acute Disease
  • Acyclic Monoterpenes
  • Analgesics / administration & dosage
  • Analgesics / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Carrageenan
  • Dinoprostone
  • Dose-Response Relationship, Drug
  • Glutamic Acid
  • Hot Temperature
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Male
  • Monoterpenes / administration & dosage
  • Monoterpenes / pharmacology*
  • Rats
  • Rats, Wistar
  • Touch


  • Acyclic Monoterpenes
  • Analgesics
  • Monoterpenes
  • Glutamic Acid
  • Carrageenan
  • linalool
  • Dinoprostone