title: Evidence for the involvement of ionotropic glutamatergic receptors on the antinociceptive effect of (-)-linalool in mice.
abstract: (-)-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.
authors.affiliation: Department of Pharmacology, Center of Biological Science, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
authors.forename: Patrícia Aparecida
authors.initials: PA
authors.lastname: Batista
authors.forename: Maria Fernanda de Paula
authors.initials: MF
authors.lastname: Werner
authors.forename: Erica Carvalho
authors.initials: EC
authors.lastname: Oliveira
authors.forename: Leonel
authors.initials: L
authors.lastname: Burgos
authors.forename: Patricia
authors.initials: P
authors.lastname: Pereira
authors.forename: Lucimar Filot da Silva
authors.initials: LF
authors.lastname: Brum
authors.forename: Adair Roberto Soares Dos
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000080462:Acyclic Monoterpenes; D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000008:administration & dosage* / Q000737:chemistry; D010147:Pain Measurement / Q000187:drug effects; D017470:Receptors, Glutamate / Q000502:physiology*
chemical_list: D000080462:Acyclic Monoterpenes; D000700:Analgesics; D018690:Excitatory Amino Acid Agonists; D039821:Monoterpenes; D017470:Receptors, Glutamate; D018698:Glutamic Acid; C018584:linalool