Enhanced anxiolytic and analgesic effectiveness or a better safety profile of morphine and tramadol combination in cholestatic and addicted mice

The involvement of the opioidergic system on anxiolytic and antinociceptive responses induced by cholestasis was investigated in cholestatic and addicted mice. Elevated plus-maze and tail-flick devices were used to assess anxiety and pain levels, respectively. The data indicated that induction of cholestasis and injection of opioid drugs including morphine and tramadol enhanced %OAT and %OAE but naloxone reduced %OAT and %OAE in the sham-operated and bile duct ligation (BDL) mice. Induction of cholestasis and addiction to morphine and tramadol prolonged tail-flick latency, which was reversed by naloxone. Coadministration of morphine and tramadol enhanced anxiolytic and analgesic effects in the sham-operated and BDL mice. It seems (a) cholestasis and addiction affect anxiety and pain behaviors, (b) mu-opioid receptors play a key role in anxiolytic and analgesic effects induced by cholestasis, and (c) cotreatment with morphine and tramadol augmented the effectiveness of them for induction of anxiolytic and analgesic effects both in cholestatic and addicted mice.

Automated summary

The involvement of the opioidergic system in the anxiolytic and antinociceptive responses induced by cholestasis was investigated. The results suggest that cholestasis and addiction can impact anxiety and pain behaviors, with mu-opioid receptors playing a key role in the anxiolytic and analgesic effects induced by cholestasis. Additionally, coadministration of morphine and tramadol can enhance these effects in both cholestatic and addicted mice.