The characteristics of the anti-inflammatory action of sodium diclofenac in cold and normal environment

Abstract

Aim. To determine the effect of low temperature and the resulting hypothermia on the anti-inflammatory activity of classical NSAID – sodium diclofenac on the model of carrageenan-induced paw edema in mice.

Materials and methods. The model of exudative inflammation – carragenin-induced paw edema was used. Mice were given an injection into the plantar aponeurosis of the left hind paw with 0.05 ml of a 1 % carrageenan solution. Sodium diclofenac was administered as a suspension intragastrically for 30 minutes before carrageenan in an effective frigoprotective dose of 14 mg/kg. The study was performed in three temperature regimes: 1) at a constant temperature +22 °C; 2) during cold exposure of animals (+10 °C) for 3 hours after the carrageenan injection; 3) during cold exposure of animals (+10 °С) for 3 hours before and 3 hours after carrageenan injection. The severity of the inflammatory reaction was evaluated by the increase in the mass of the paws of animals. The anti-inflammatory activity of sodium diclofenac was determined by the ability to reduce the mass of the edematous limb compared to the untreated control. To assess the severity of hypothermia, the body temperature of animals was measured using an infrared thermometer.

Results and discussion. At a temperature of 22 °C, carrageenan increased the median paw mass by 84 mg (73 %), sodium diclofenac decreased its growth by 22.5 mg (16.5 %). It indicates the inherent anti-inflammatory effect of this drug. In regime 2 the phlogogenic effect of carrageenan persisted, but its severity was significantly less (p ≤ 0.01) – the increase in paw mass was only 54.5 mg (44 %). Under these conditions, the anti-inflammatory effect of diclofenac was absent – the mass of the edematous paw increased by 51.5 mg (42 %). In regime 3 the pro-inflammatory effect of carrageenan was even weaker: the mass of the edematous paw increased by only 42.5 mg (36 %), sodium diclofenac also did not show the anti-inflammatory effect under these conditions, increasing the median paw mass by 42.5 mg (32 %). Sodium diclofenac significantly reduced the degree of hypothermia in regimes 2 and 3, confirming the presence of frigoprotective properties. The relationship between the degree of hypothermia and the severity of the inflammatory reaction was analyzed.

Conclusions. The pro-inflammatory effect of carrageenan decreases with hypothermia. Sodium diclofenac exhibits frigoprotective properties, reducing the severity of hypothermia. The anti-inflammatory effect of the drug on the model of carrageenan-induced paw edema disappears at low temperatures.