Clinical studies have demonstrated that when
opiates are used to control
cancer pain, psychological dependence and
analgesic tolerance are not a major concern. The present study was, therefore, designed to investigate the modulation of rewarding effects of
opiates under inflammatory
chronic pain in SD rats.
Formalin (2.5%, 50 microliters) or
carrageenan (1%, 100 microliters) was injected into the plantar surface of the rat paw.
Formalin and
carrageenan reduced the paw pressure threshold. The
hyperalgesia lasted for 9 to 13 days. Rewarding effect of
morphine was evaluated by conditioned place preference paradigm.
Morphine produced a significant place preference. This effect was significantly attenuated in inflamed groups as compared with the respective non-inflamed groups. Furthermore, the
morphine-induced place preference in the inflamed group gradually recovered to the respective control level as the
inflammation healed. On the other hand, we found that
kappa-opioid receptor agonists markedly inhibit rewarding effect of
mu-opioid receptor agonists. Therefore, to elucidate the mechanism of this attenuation, the effects of pretreatment with kappa- and
delta-opioid receptor antagonists,
nor-binaltorphimine (
nor-BNI) and
naltrindole (NTI), on the development of the
morphine-induced place preference under
inflammation were examined.
Nor-BNI, but not NTI, eliminated the suppression of the
morphine-induced place preference in inflamed groups. The
morphine-induced increase in
dopamine turnover in the limbic forebrain was suppressed under
inflammation, and the suppression was abolished by the pretreatment with
nor-BNI. These results suggest that endogenous kappa-
opioid systems may be activated by chronic inflammatory nociception, resulting in the suppression of the development of rewarding effects produced by
morphine.