Abstract
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 morphine, fentanyl and oxycodone under inflammatory and neuropathic pain state in rodents. Rewarding effect of these opioids was evaluated by conditioned place preference paradigm. These opioids produced a significant place preference in non-inflamed and sham groups. This effect was significantly attenuated in inflamed and ligated groups as compared with the respective non-inflamed and sham groups. On the other hand, we found that the morphine-induced increase in dopamine release in the nucleus accumbens (N.Acc) was suppressed under inflammation, and the suppression was abolished by the pretreatment with κ receptor antagonist and antibody to dynorphin. These results suggest that endogenous κ-opioidergic system may be activated by chronic inflammatory nociception, resulting in the suppression of the development of rewarding effects produced by opioids. Furthermore, we demonstrated that a state of neuropathic pain induced by sciatic nerve ligation leads to the reduction in the μ-receptor function in the ventral tegmental area. This effect produces a significant decrease in the opioid-induced DA release in the N.Acc, resulting in the inhibition of rewarding effect of opioid in rats. These findings strongly indicate that treatment of opioids could be highly recommended for the relief of severe chronic pain.
