(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.