α-Terpineol (TPN), a volatile monoterpene alcohol, is relatively non-toxic and one of the major components of the essential oils of various plant species. In this study, we tested for the antihypernociceptive activity of TPN (25, 50 or 100 mg/kg, i.p.) in mice using mechanical models of hypernociception induced by carrageenan (CG, 300 μg/paw) and the involvement of important mediators of its cascade signalling, such as tumour necrosis factor-α (TNF-α, 100 pg/paw), prostaglandin E₂ (PGE₂, 100 ng/paw) or dopamine (DA, 30 μg/paw). We also investigated the anti-inflammatory effect of TPN on the model of carrageenan-induced pleurisy and the LPS-induced nitrite production in murine macrophages. Pre-systemic treatment with TPN (25, 50 or 100 mg/kg, i.p.) inhibited the development of mechanical hypernociception induced by CG or TNF-α. A similar effect was also observed upon PGE₂ and DA administration. In addition, TPN significantly inhibited the neutrophil influx in the pleurisy model. TPN (1, 10 and 100 μg/mL) also significantly reduced (p < 0.01) nitrite production in vitro. Our results provide information about the antinociceptive and anti-inflammatory properties of TPN on mechanical hypernociception and suggest that this compound might be potentially interesting in the development of new clinically relevant drugs for the management of painful and/or inflammatory disease.

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