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

Pain. 1988 Nov;35(2):179-186. doi: 10.1016/0304-3959(88)90225-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzeneacetamides*
  • Inflammation / complications*
  • Male
  • Morphine / pharmacology
  • Motivation / drug effects*
  • Narcotics / pharmacology*
  • Narcotics / therapeutic use
  • Pain / etiology
  • Pain / metabolism
  • Pain / psychology*
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / physiology*
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu


  • Benzeneacetamides
  • Narcotics
  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Morphine
  • U 69593