long-term morphine-treated rats are more sensitive to antinociceptive effect of diclofenac than the morphine-naive rats

this study investigates the effectiveness of the antinociceptive effects of diclofenac, an nsaid, on the nociceptive behavior of morphine-treated rats on formalin test.rats were treated with morphine-containing drinking water for twenty one days, which induced morphine dependence. the antinociceptive effects of 8, 16, and 32 mg/kg doses of diclofenac were then evaluated and compared with distilled water in a formalin-based model of pain.diclofenac potentiated pain suppression in morphine-dependent rats during the interphase of the formalin test and reduced the pain score during phase ii. the post-test analysis revealed that both 16 mg/kg (p < 0.0001) and 32 mg/kg (p < 0.0001) doses of diclofenac had a significant effect on the interphase, while 8 mg/kg (p < 0.05), 16 mg/kg (p < 0.05), and 32 mg/kg                      (p < 0.01) doses of diclofenac significantly affected phase ii. in contrast, the antinociceptive effects of diclofenac on morphine-naïve rats were observed during phase ii only with the a 32 mg/kg dose (p < 0.05).in general, these results suggest that the long-term use of morphine in rats increases their sensitivity to the antinociceptive effects of diclofenac. furthermore, the results support the existence of a non-opioid-dependent mechanism of pain suppression during the interphase of formalin test.