Evidence for the involvement of ionotropic glutamatergic receptors on the antinociceptive effect of (-)-linalool in mice

Neurosci Lett. 2008 Aug 8;440(3):299-303. doi: 10.1016/j.neulet.2008.05.092. Epub 2008 Jun 24.


(-)-Linalool is a monoterpene alcohol which is present in the essential oils of several aromatic plants. Recent studies suggest that (-)-linalool has anti-inflammatory, antihyperalgesic and antinociceptive properties in different animal models. The present study investigated the contribution of glutamatergic system in the antinociception elicited by (-)-linalool in mice. Nociceptive response was characterized by the time that the animal spent licking the injected hind paw or biting the target organ following glutamate receptor agonist injections. (-)-Linalool administered by intraperitoneal (i.p., 10-200 mg/kg), oral (p.o., 5-100 mg/kg) or intrathecal (i.t., 0.1-3 microg/site) routes dose-dependently inhibited glutamate-induced nociception (20 micromol/paw, pH 7.4) with ID(50) values of 139.1 mg/kg; 34.6 mg/kg; and 0.9 microg/site, with inhibitions of 70+/-4; 72+/-7 and 74+/-8%, respectively. However, the intraplantar injection of (-)-linalool partially (49+/-9%) inhibited glutamate-induced nociception. Furthermore, (-)-linalool (200 mg/kg) given i.p. also reduced significantly the biting response caused by intrathecal injection of glutamate (30 microg/site), AMPA (25 ng/site), SP (135 ng/site), NMDA (25 ng/site) and kainate (23.5 ng/site), with inhibitions of 89+/-6%, 73+/-11%, 85+/-4%, 98+/-2% and 52+/-15%, respectively. However, (-)-linalool did not inhibit nociception induced by intrathecal injection of trans-ACPD (8.6 microg/site). Taken together, these results provide experimental evidences indicating that (-)-linalool produce marked antinociception against glutamate induced pain in mice, possible due mechanisms operated by ionotropic glutamate receptors, namely AMPA, NMDA and kainate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclic Monoterpenes
  • Analgesics / administration & dosage*
  • Analgesics / chemistry
  • Animals
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Excitatory Amino Acid Agonists / pharmacology
  • Glutamic Acid
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Male
  • Mice
  • Monoterpenes / administration & dosage*
  • Monoterpenes / chemistry
  • Pain Measurement / drug effects
  • Receptors, Glutamate / physiology*


  • Acyclic Monoterpenes
  • Analgesics
  • Excitatory Amino Acid Agonists
  • Monoterpenes
  • Receptors, Glutamate
  • Glutamic Acid
  • linalool