Although mu-
opioids such as
morphine are undoubtedly effective in the treatment of acute and
postoperative pain, kappa-
opioids are of interest for the modulation of
visceral pain. In the present study, we compared a kappa-
opioid agonist (
U50488-H; 0.63-40 mg/kg) with a mu-
opioid agonist (
morphine; 0.63-40 mg/kg) in different
pain models (tail withdrawal, writhing,
formalin and plantar test) to represent acute, peritoneovisceral and inflammatory
pain states in rats. The effects of the respective receptor agonists on gastrointestinal motility,
muscle rigidity and abuse liability were also studied in appropriate animal models (
charcoal,
castor oil, rotarod and
drug discrimination learning).
Morphine was highly efficacious in all the nociceptive models employed, but also elicited a potent inhibition of gastric motility, caused severe
muscle rigidity and locomotor disturbances and displayed a potential for abuse liability at the higher doses tested (> or =10 mg/kg
morphine). In contrast, U50488-H was inactive in the tail withdrawal test, but was more effective in visceral and inflammatory
pain settings. Although U50488-H did not elicit any gastrointestinal inhibition, a loss of muscle tone following administration of the compound led to detrimental effects on rotarod performance. The findings presented here indicate that kappa-
opioids possess antinociceptive efficacy in visceral and inflammatory
pain settings, but their administration can lead to a loss of muscle tone. In contrast, mu-
opioids are highly active as
analgesics against a range of nociceptive stimuli, but also concomitantly elicit strongly adverse effects.