Synergistic interaction between docosahexaenoic acid and diclofenac on inflammation, nociception, and gastric security models in rats

The addition of polyunsaturated fatty acids to nonsteroidal anti-inflammatory drugs can increase their antinociceptive activity and produce a gastroprotective effect. The aim of the present study was to examine the effects of the interaction between docosahexaenoic acid (DHA) and diclofenac on inflammation (fixed ratios 1:1, 1:3, and 3:1), nociception (fixed ratio 1:3), and gastric injury in rats. DHA, diclofenac, or combinations of DHA and diclofenac produced anti-inflammatory and antinociceptive effects in rat. The administration of diclofenac produced significant gastric damage, but this effect was not observed with either DHA or the DHA-diclofenac combinations. Effective dose (ED30) values were estimated for each individual drug and analyzed isobolographically. The anti-inflammatory experimental ED30 values were 6.97mg/kg (1:1 fixed ratio), 1.1 mg/kg (1:3 fixed ratio), and 11.34mg/kg (3:1 fixed ratio). These values were significantly lower (p< .05) than the theoretical ED30 values: 67.94mg/kg (1:1), 35.37mg/kg (1:3), and 100.51mg/kg (3:1). The antinociceptive experimental value was 1.25mg/kg (1:3 fixed ratio). This value was lower (p<.05) than the theoretical ED30, which was predicted to be 15.92mg/kg. These data indicate that the DHA-diclofenac combinations interact at the systemic level, produce minor gastric damage, and potentially have therapeutic advantages for the clinical treatment of inflammatory pain.