Opioids are the most effective drugs used for the management of moderate to severe
pain; however, their chronic use is often associated with numerous adverse effects. Some results indicate the involvement of oxidative stress as well as of
proteasome function in the development of some
opioid-related side effects including
analgesic tolerance,
opioid-induced
hyperalgesia (OIH) and dependence. Based on the evidence, this study investigated the impact of
morphine,
buprenorphine or
tapentadol on intracellular
reactive oxygen species levels (ROS),
superoxide dismutase activity/gene expression, as well as β2 and β5 subunit
proteasome activity/biosynthesis in SH-SY5Y cells. Results showed that tested
opioids differently altered ROS production and SOD activity/biosynthesis. Indeed, the increase in ROS production and the reduction in SOD function elicited by
morphine were not shared by the other
opioids. Moreover, tested drugs produced distinct changes in β2(trypsin-like) and β5(chymotrypsin-like)
proteasome activity and biosynthesis. In fact, while prolonged
morphine exposure significantly increased the proteolytic activity of both subunits and β5
mRNA levels,
buprenorphine and
tapentadol either reduced or did not alter these parameters. These results, showing different actions of the selected
opioid drugs on the investigated parameters, suggest that a low µ receptor intrinsic efficacy could be related to a smaller oxidative stress and
proteasome activation and could be useful to shed more light on the role of the investigated cellular processes in the occurrence of these
opioid drug side effects.