The individual and combined effects of U50,488, and flurbiprofen axetil on visceral pain in conscious rats.

We examined the effects of U50,488, a kappa-opioid receptor agonist, and flurbiprofen axetil, a nonsteroidal antiinflammatory drug, in a visceral pain model using conscious rats. U50,488 produced visceral antinociception, but exaggerated the adverse effects on the central nervous system (CNS) at 0.9 mg/kg or more. Naloxone completely antagonized these effects. Flurbiprofen axetil produced visceral antinociception, but exaggerated the adverse effects on the CNS at 80 mg/kg. Coadministration of U50,488 (0.27 mg/kg) and flurbiprofen axetil (50 mg/kg) produced intense visceral antinociception without adverse effects on the CNS, implying therapeutic efficacies of coadministration of kappa-opioid receptor-agonists and nonsteroidal antiinflammatory drugs on visceral pain.