Chemical Composition and Evaluation of the Anti-Hypernociceptive Effect of the Essential Oil Extracted from the Leaves of Ugni myricoides on Inflammatory and Neuropathic Models of Pain in Mice

The study analyzes the chemical composition of the essential oil obtained from the leaves of Ugni myricoides (Kunth) O. Berg (U. myricoides EO). The composition of the essential oil was characterized by GC-FID and GC-MS analysis, showing at least six major constituents: alpha-pinene (52.1%), 1,8-cineole (11.9%), alpha-humulene (4.6%), caryophyllene oxide + globulol (4.5%), humulene epoxide II (4.2%) and beta-caryophyllene (2.9%). It demonstrates for the first time the systemic anti-hypernociceptive properties of this orally administered oil in inflammatory and neuropathic models of hypernociception in mice. The effects of U. myricoides EO and its major constituent, alpha-pinene, were compared with those of indomethacin or gabapentin, drugs used clinically to treat inflammatory and neuropathic processes. Like indomethacin (5 or 10 mg/kg, p.o.), U. myricoides EO (5-50 mg/kg, p.o.) was able to significantly prevent mechanical hypernociception induced by carrageenan or complete Freund's adjuvant (CFA) in mice. These effects were observed for up to 48 h after i.pl. injection of flogistic agents. Repeated treatment with U. myricoides EO (5-25 mg/kg, p.o.), alpha-pinene (5-50 mg/kg, p.o.), or gabapentin (70 mg/kg, p.o.) also abolished the mechanical sensitization induced by CFA, or following the partial ligation of the sciatic nerve (PLSN). The present results indicate that U. myricoides EO produces marked anti-hypernociceptive effects in carrageenan and CFA mechanical sensitization models, and also inhibited neuropathic pain-like behavior after PLSN with efficacy similar to that observed for indomethacin or gabapentin. The relevant effects shown by U. myricoides EO are related, at least in part, to the presence of alpha-pinene and may be of potential interest for the management of inflammatory and neuropathic pain.