Mechanisms of opioid receptor desensitisation in single neurons

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Opioid drugs including morphine and codeine are the most effective analgesics known but their utility is limited by problems of tolerance (which is the need for increasing doses of drug to achieve the same effect), physical dependence characterised by a debilitating withdrawal syndrome on cessation of use, and addiction or compulsive drug seeking and use. Better understanding of the mechanisms underlying these adverse processes could lead to the development of more acceptable pain relieving agents. This project will increase understanding of the initial molecular events occurring in nerve cells that are believed to underlie the development of tolerance and physical dependence on opioid drugs. These studies will focus on sensory nerve cells isolated and cultured from animals, which are one of the major targets of pain relieving drugs. Understanding of these processes will lead to development of better strategies to avoid development of tolerance and perhaps physical dependence. They will also identify on a molecular level the mechanisms that determine why one opioid drug may produce more tolerance than another. This knowledge may lead to the development of pain relieving drugs that do not so readily lose their effectiveness in the management of chronic pain.