Evaluation of the antinociceptive effect of Rosmarinus officinalis L. using three different experimental models in rodents.

The rationale of this investigation was to examine the antinociceptive effect of an ethanol extract of Rosmarinus officinalis (RO) aerial parts, using three different experimental models: acetic acid-induced writhing test and formalin test in mice; and a model of arthritic pain: "pain-induced functional impairment model in the rat (PIFIR model)". The antinociceptive efficacies were evaluated using several dose-response curves and time courses. The antinociceptive effects from RO extract were compared with the antinociceptive effect of either tramadol (TR: 3.16-50 mg/kg, i.p. in mice, and 1.0-31.62 mg/kg, i.p. in rats) or acetylsalicylic acid (AA: 31.62-562.32 mg/kg, p.o.). RO extract (10-300 mg/kg, p.o.) significantly (P < 0.001) reduced the number of writhing movement induced by the i.p. administration of acetic acid solution in a dose-dependent way (ED50 = 108.84 mg/kg, whereas, TR showed an ED50 = 12.38 mg/kg). In addition, RO extract (30-300 mg/kg) significantly (P < 0.001) inhibited licking and shaking behaviours in both early (neurogenic pain) and in the late (inflammatory pain) phases of the formalin test. These effects were like those produced by TR. Concerning the results using the PIFIR model, RO extract (30-3000 mg/kg, p.o.) like either TR or AA, produced a significant (P < 0.001) and dose-dependent antinociceptive response in rats (RO: ED50 = 222.78 mg/kg versus TR: ED50 = 11.06 mg/kg and AA: ED50 = 206.13 mg/kg). These results strongly suggest that aerial parts of RO possess antinociceptive and anti-inflammatory activity, and reinforce the use of this plant in folk medicine.

Usefulness of the pain-induced functional impairment model to relate plasma levels of analgesics to their efficacy in rats.

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.