Screening of the action mechanisms involved in the antinociceptive effect of isopulegol and its complex in cyclodextrin using acute nociception models in mice

Abstract

Isopulegol, a terpene compound commonly present in the essential oils of several aromatic plants, may present a number of important pharmacological activities. Besides the screening of the antinociceptive effect of the monoterpene isopulegol (ISO) and its inclusion complex in β-cyclodextrins (ISO/CD), this study also aimed at investigating the signaling pathways involved in the antinociceptive response. The effects of ISO and ISO/CD on the central nervous system (CNS) were evaluated through open-field and rota-rod assays and the antinociceptive effects in formalin models, abdominal contortions by acetic acid, hot-plate and plantar mechanical hypernociception. Male and female mice (Mus musculus), weighing between 20–30 g, were divided into 6-animal groups. The oral administration of isopulegol and its complex showed significant antinociceptive effects in the 10, 5 and 1 mg/kg doses for both the formalin and abdominal contortion assays, with highlights on the 10 mg/kg dose of ISO and ISO/CD in both assays. Likewise, the 10 mg/kg dose was selected for the evaluation of the effects on the CNS, central and peripheral antinociceptive effect and screening of the signaling pathways involved in the analgesic potential. ISO and ISO/CD, both in the 10 mg/kg dose v.o., did not show any alteration to the parameters evaluated of the CNS and the results pointed to a possible acute antinociceptive action in the tests of formalin, abdominal contortion, hot-plate and plantar mechanical hypernociception, suggesting the involvement of these signaling pathways: opioid, potassium channel, cholinergic, nitric oxide, cyclic guanosin monophosphate, vaniloid and glutamatergic. The results suggest that ISO and ISO/CD carry a promising antinociceptive potential as a possible alternative to the pharmacological treatment of pain, showing that the inclusion of ISO in cyclodextrins enhance its pharmacological properties, once that the complexation process involves much lower amounts of the compound – what contributes to a better bioavailability and weaker probability for the development of undesired effects.