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a-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 lg/paw) and the involvement of important mediators of its cascade signalling, such as tumour necrosis factor-a (TNF-a, 100 pg/paw), prostaglandin E 2 (PGE 2 , 100 ng/paw) or dopamine (DA, 30 lg/paw). We also investigated the anti-inflammatory effect of TPN on the model of carra-geenan-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-a. A similar effect was also observed upon PGE 2 and DA administration. In addition, TPN significantly inhibited the neutrophil influx in the pleurisy model. TPN (1, 10 and 100 lg/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.

(2015) The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines, Pharmaceutical Biology, 53:11, 1583-1590, DOI: 10.3109/13880209.2014 To link to this article: https://doi.org/10. 3109/13880209.2014.993040 Published online: 05 May 2015.Submit your article to this journal Objective: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action. Materials and methods: Mice treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30-180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1-8 h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence.Results: PC reduced (p50.001) the hyperalgesia induced by carrageenan, TNF-a, dopamine, and PGE 2 . PC decrease total leukocyte migration (100 mg/kg: p50.01), neutrophils (50 and 100 mg/kg: p50.05 and 0.001), and TNF-a (25, 50, and 100 mg/kg: p50.01, 0.05, and 0.001, respectively), besides reducing NO production (p50.05) in vitro. PC produced antinociceptive effect in tail-flick test (p50.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p50.001) the number of c-Fos-immunoreactive neurons in PAG. Discussion and conclusion: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.

This study investigated the possible antinociceptive effect of p-cymene in different tests of orofacial nociception. The animals (mice) were pretreated (i.p.) with p-cymene (25, 50, 100 mg/kg), morphine (5 mg/kg), or vehicle (0.2% Tween 80+saline), and were then subsequently administered, subcutaneously into their upper lip: formalin, capsaicin, and glutamate. The nociceptive behavior response was characterized by the time in s that the mice remained rubbing the orofacial region, for a period of 40 min in the formalin test (first phase, 0-6 min; and second phase, 21-40 min), and for 42 and 15 min in the capsaicin and glutamate tests, respectively. To verify the possible opioid involvement in the antinociceptive effects, naloxone (i.p.) was administered into the mice 15 min prior to the pretreatment with p-cymene (100 mg/kg). Finally, whether or not the p-cymene evoked any change in motor performance in the Rota-rod test was evaluated. The results showed that the treatment with p-cymene, at all doses, reduced (p<0.001) the nociceptive behavior in all nociception tests. The antinociceptive effect of p-cymene was antagonized by naloxone (1.5 mg/kg). Additionally, mice treated with p-cymene did not show any change in motor performance. In conclusion, p-cymene attenuated orofacial nociception, suggesting an involvement of the opioid system in this effect. Thus, p-cymene might represent an important biomolecule for management and/or treatment of orofacial pain.

In this study, we describe the antinociceptive activity of the ethanol extract (EE), chloroform (CF) and methanol (MF) fractions obtained from Sida cordifolia, popularly known in Brazil as "malva branca" or "malva branca sedosa". Leaves of S. cordifolia were used to produce the crude ethanol extract and after CF and MF. Experiments were conducted on Swiss mice using the glutamate and formalin-induced orofacial nociception. In the formalin test, all doses of EE, CF and MF significantly reduced the orofacial nociception in the first (p < 0.001) and second phase (p < 0.001), which was also naloxone-sensitive. In the glutamate-induced nociception test, only CF and MF significantly reduced the orofacial nociceptive behavior with inhibition percentage values of 48.1% (100 mg/kg, CF), 56.1% (200 mg/kg, CF), 66.4% (400 mg/kg, CF), 48.2 (200 mg/kg, MF) and 60.1 (400 mg/kg, MF). Furthermore, treatment of the animals with EE, CF and MF was not able to promote motor activity changes. These data demonstrate that S. cordifolia has a pronounced antinociceptive activity on orofacial nociception. However, pharmacological and chemical studies are necessary in order to characterize the responsible mechanisms for this antinociceptive action and also to identify other bioactive compounds present in S. cordifolia.