title: Profile of spinal and supra-spinal antinociception of (-)-linalool.
abstract: We previously reported that administration of (-)-linalool, the naturally occurring enantiomer in essential oils, induced a significant reduction in carrageenin-induced oedema and in acetic acid-induced writhing. The latter effect was completely antagonised by the muscarinic receptor antagonist atropine and by the opioid receptor antagonist naloxone. To further characterise the antinociceptive profile of (-)-linalool, we studied its effect in the hot plate and the formalin in tests. In addition, to determine the possible involvement of the cholinergic, opioidergic and dopaminergic systems, we tested the effects of atropine, pirenzepine, a muscarinic M1 receptor antagonist, naloxone, sulpiride, a dopamine D2 receptor antagonist and (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH-23390), a dopamine D1 receptor antagonist on (-)-linalool-induced antinociception. Moreover, since K(+) channels seem to play an important role in the mechanisms of pain modulation, we examined the effect of glibenclamide, an ATP-sensitive K(+) channel inhibitor on (-)-linalool-induced antinociception. The administration of (-)-linalool (100 and 150 mg/kg, s.c.) increased the reaction time in the hot-plate test. Moreover, (-)-linalool (50 and 100 mg/kg) produced a significant reduction in the early acute phase of the formalin model, but not in the late tonic phase. The highest dose (150 mg/kg) caused a significant antinociceptive effect on both phases. The antinociceptive effects of (-)-linalool were decreased by pre-treatment with atropine, naloxone, sulpiride and glibenclamide but not by pirenzepine and SCH-23390. These results are in agreement with the demonstrated pharmacological properties of linalool, mainly its cholinergic, local anaesthetic activity and its ability to block NMDA receptors. Furthermore, a key role seems to be played by K(+) channels, whose opening might be the consequence of a stimulation of muscarinic M2, opioid or dopamine D2 receptors.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Sassari, via Muroni 23/a, 07100 Sassari, Italy. apeana@uniss.it
authors.forename: Alessandra T
authors.initials: AT
authors.lastname: Peana
authors.forename: M Graziella
authors.initials: MG
authors.lastname: De Montis
authors.forename: Eugenio
authors.initials: E
authors.lastname: Nieddu
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Spano
authors.forename: Paolo S
authors.initials: PS
authors.lastname: D'Aquila
authors.forename: Proto
authors.initials: P
authors.lastname: Pippia
mesh_terms: D000080462:Acyclic Monoterpenes; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
chemical_list: D000080462:Acyclic Monoterpenes; D000700:Analgesics; D018492:Dopamine Antagonists; D039821:Monoterpenes; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; C018584:linalool