Abstract:The present study investigated the antinociceptive effects of Ocimum basilicum L. (Lamiaceae) leaf essential oil (LEO) and (-)-linalool (LIN) in formalin (2%)-, glutamate (25 μM)-and capsaicin (2.5 µg)-induced orofacial nociception models in mice. The involvement of these substances was further evaluated on the neuronal excitability of the hippocampal dentate gyrus. Male mice (n=8/group) were pretreated separately with LEO and by LIN (50, 100, and 200 mg/kg, i.p.), morphine (5 mg/kg, i.p.) and vehicle (saline + Tween 80 0.2%), before injection of nociceptive agent into the right upper lip (perinasal area). The LEO and LIN reduced the nociceptive face-rubbing behaviour in both phases on formalin test. LEO and LIN, at high doses, produced significantly antinociceptive effect in the capsaicin and glutamate tests. In hippocampal slices, LEO inhibited the population spike generated by stimulation of the hylus (antidromic stimulation), with an IC50 of 0.1±0.05 mg/mL. This response was reversibly blocked by lidocaine (0.5 mg/mL), a known voltage-dependent sodium channel antagonist and by LIN (0.5 mg/mL). Our results suggest that LEO and LIN modulate neurogenic and inflammatory pain in the tests of orofacial nociception induced by formalin, capsaicin and glutamate. Part of these effects may be associated with decreased peripheral and central neuronal excitability.

The lizard cortex has remarkable similarities with the mammalian hippocampus. Both regions process memories, have similar cytoarchitectural properties, and are important neurogenic foci in adults. Lizards show striking levels of widespread neurogenesis in adulthood and can regenerate entire cortical areas after injury. Nitric oxide (NO) is an important regulatory factor of mammalian neurogenesis and hippocampal function. However, little is known about its role in nonmammalian neurogenesis. Here, we analyzed the distribution, morphology, and dendritic complexity (Neurolucida reconstructions) of NO-producing neurons through NADPH diaphorase (NADPHd) activity, and how they compare with the distribution of doublecortin-positive (DCX+) neurons in the hippocampal formation of the neotropical lizard Tropidurus hispidus. NADPHd-positive (NADPHd+) neurons in the dorsomedial cortex (DMC; putatively homologous to mammalian CA3) were more numerous and complex than the ones in the medial cortex (MC; putatively homologous to the dentate gyrus). We found that NADPHd+ DMC neurons send long projections into the MC. Interestingly, in the MC, NADPHd+ neurons existed in 2 patterns: small somata with low intensity of staining in the outer layer and large somata with high intensity of staining in the deep layer, a pattern similar to the mammalian cortex. Additionally, NADPHd+ neurons were absent in the granular cell layer of the MC. In contrast, DCX+ neurons were scarce in the DMC but highly numerous in the MC, particularly in the granular cell layer. We hypothesize that NO-producing neurons in the DMC provide important input to proliferating/migrating neurons in the highly neurogenic MC.

The racemate linalool and its levogyrus enantiomer [(−)-LIN] are present in many essential oils and possess several pharmacological activities, such as antinociceptive and anti-inflammatory. In this work, the effects of essential oil obtained from the cultivation of the Ocimum basilicum L. (EOOb) derived from Germplasm Bank rich in (−)-LIN content in the excitability of peripheral nervous system were studied. We used rat sciatic nerve to investigate the EOOb and (−)-LIN effects on neuron excitability and the extracellular recording technique was used to register the compound action potential (CAP). EOOb and (−)-LIN blocked the CAP in a concentration-dependent way and these effects were reversible after washout. EOOb blocked positive amplitude of 1st and 2nd CAP components with IC50 of 0.38 ± 0.2 and 0.17 ± 0.0 mg/mL, respectively. For (−)-LIN, these values were 0.23 ± 0.0 and 0.13 ± 0.0 mg/mL. Both components reduced the conduction velocity of CAP and the 2nd component seems to be more affected than the 1st component. In conclusion EOOb and (−)-LIN inhibited the excitability of peripheral nervous system in a similar way and potency, revealing that the effects of EOOb on excitability are due to the presence of (−)-LIN in the essential oil.

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