Motivational effects of opioids in an animal model of prolonged inflammatory pain: alteration in the effects of kappa- but not of mu-receptor agonists.

An unbiased preference conditioning procedure was used to characterize and compare the motivational effects of opioids in naive rats and those suffering from the prolonged pain associated with Freund's adjuvant (FA)-induced inflammation of one hind limb. The mu-opioid agonist morphine functioned as a reinforcer in naive animals, producing marked preferences for the drug-paired place. Similarly, rats injected with FA 7 days prior to conditioning exhibited a preference for the morphine place, and the magnitude of this effect did not differ between groups. Administration of the kappa-opioid receptor agonist U-69593 to naive rats produced dose-related place aversions. The aversive effect of this kappa-agonist was, however, abolished in FA-treated rats. Thus, regardless of the dose administered, U-69593 produced conditioning similar to that observed in response to saline. These data suggest that kappa-agonists may lack aversive effects in subjects experiencing prolonged noxious stimulation, and as such may be effective therapeutic agents in the management of chronic pain states.