title: β-Cyclodextrin-complexed (-)-linalool produces antinociceptive effect superior to that of (-)-linalool in experimental pain protocols.
abstract: Many plants produce (-)-linalool, a plant-derived monoterpene alcohol, including members of the Lamiaceae (mints) and Lauraceae family (laurels, cinnamon, rosewood). The anti-inflammatory and analgesic effects of (-)-linalool have been widely suggested for various studies. Poor chemical stability and short half-life restrain the clinical applications of some essential oil and monoterpenes, including (-)-linalool. However, β-cyclodextrin (β-CD) has been used to increase solubility and stability of lipophilic compounds and also to improve the pharmacological effects. In this study, the antinociceptive effect of (-)-linalool and (-)-linalool/β-CD was examined using the acetic acid writhing reflex, formalin and hotplate tests in rodents. (-)-Linalool and (-)-linalool/β-CD demonstrated strong antinociceptive activity in all the chemical- and heat-induced mice models (p < 0.01 or p < 0.001). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. In peritonitis induced by carrageenan, isolated monoterpene or β-CD complex also reduced total leucocyte migration and TNF-α levels in peritoneal fluid. The inclusion complexes, (-)-linalool/β-CD, revealed that the antinociceptive effect was significantly (p < 0.01) improved when compared with (-)-linalool alone. Such results were unlikely to be provoked by any motor abnormality. Together, our results suggest that β-CD might represent an important tool for improvement of analgesic and anti-inflammatory profiles of (-)-linalool and other water-insoluble compounds, such as lipophilic monoterpenes or essential oils.
authors.affiliation: Department of Physiology, Federal University of Sergipe (UFS), Aracaju, Brazil. lucindo@pq.cnpq.br
authors.forename: Lucindo J
authors.initials: LJ
authors.lastname: Quintans-Júnior
authors.forename: Rosana S S
authors.initials: RS
authors.lastname: Barreto
authors.forename: Paula P
authors.initials: PP
authors.lastname: Menezes
authors.forename: Jackson R G S
authors.initials: JR
authors.lastname: Almeida
authors.forename: Ana Flávia S C
authors.initials: AF
authors.lastname: Viana
authors.forename: Rita C M
authors.initials: RC
authors.lastname: Oliveira
authors.forename: Aldeídia P
authors.initials: AP
authors.lastname: Oliveira
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gelain
authors.forename: Waldecy
authors.initials: W
authors.lastname: de Lucca Júnior
authors.forename: Adriano A S
authors.initials: AA
authors.lastname: Araújo
mesh_terms: D000080462:Acyclic Monoterpenes; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000080462:Acyclic Monoterpenes; D000700:Analgesics; D004337:Drug Carriers; D039821:Monoterpenes; D014409:Tumor Necrosis Factor-alpha; D047392:beta-Cyclodextrins; C018584:linalool