Involvement of adenosine A1 and A2A receptors in (-)-linalool-induced antinociception.

Abstract In recent studies performed in our laboratory we have shown that acute administration of (−)-linalool, the natural occurring enantiomer in essential oils, possesses anti-inflammatory, antihyperalgesic and antinociceptive effects in different animal models. The antihyperalgesic and antinociceptive effects of (−)-linalool have been ascribed to its capacity in stimulating the opioidergic, cholinergic and dopaminergic systems, as well as to its interaction with K + channels, or to its local anaesthetic activity and/or to the negative modulation of glutamate transmission. Activation of A 1 or A 2A receptors has been shown to induce antinociceptive effects, and the possible involvement of adenosine in (−)-linalool antinociceptive effect, has not been elucidated yet. Therefore, in the present study, we have investigated the effects of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A 1 receptor antagonist and the effects of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A 2A receptor antagonist on the antinociception of (−)-linalool in mice, measured in the hot-plate test. Both DPCPX (0.1 mg/kg; i.p.) and DMPX (0.1 mg/kg; i.p.) pre-treatment significantly depressed the antinociceptive effect of (−)-linalool at the highest doses tested. These findings demonstrated that the effect of (−)-linalool on pain responses is, at least partially, mediated by the activity of adenosine A 1 and A 2A receptors.