Controlling cancer pain: Is morphine the best we can do?

Despite the existence of a family of 3 classical and one non-classical opioid receptor, morphine, acting at the MOP (m) receptor remains the gold standard for use in cancer pain. The main thrust of opioid development has been to produce highly selective morphine like molecules but these produce side effects (respiratory depression and arrest, constipation, nausea and vomiting, pruritis and tolerance). Tolerance is particularly troublesome as this leads to increased dosing and more side effects. Laboratory experiments suggest that simultaneous targeting of multiple members of the opioid family may be the way forward. For example disruption of DOP (d) receptor activity reduces morphine tolerance. Rational design and evaluation of non-selective opioids might offer good quality analgesia, reduced side effects and an alternative to morphine.