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.
Formalin or
carrageenan was injected into the plantar surface of the rat paw.
Formalin and
carrageenan reduced the paw pressure threshold. The
hyperalgesia lasted for 9-13 days. The 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 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. We also found that
kappa-receptor agonists markedly inhibited the rewarding effect of
mu-receptor agonists. Therefore, to elucidate the mechanism of this attenuation, the effects of pretreatment with kappa- and
delta-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 (DA) 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, and then the activation of kappa-
opioid system may inhibit DA release in nucleus accumbens, resulting in the suppression of the development of rewarding effects produced by
morphine.