Nalbuphine ameliorates morphine/tramadol-induced dependence and tolerance to analgesia through locus coereulus (LC) norepinephrine

Abstract

Chronic use of opioids as morphine and tramadol to control pain is associated with several side effects and tolerance to  their analgesic effect and dependence. Some of the side effects of opioids can be ameliorated by naloxone, however this  is associated with decreased analgesia. Nalbuphine was shown to ameliorate morphine and tramadol psychological  dependence. The current study aims to investigate the effect of co-administration of nalbuphine with morphine or tramadol on tolerance to analgesia and physical dependence and the possible involvement of  norepinephrine in its effect. Co-admistration of nalbuphine with morphine or tramadol prevented tolerance to analgesia and physical dependence that was observed with each drug alone and this was associated with prevention of the  elevation in norepinephrine in the locus coereulus (LC) following naloxone administration. These results emphasize the  possible use of nalbuphine in combination with morphine or tramadol to preserve their analgesic effect and to prevent  the development of dependence to their effect.