Differentiation of multiple phenotypes of rostral ventromedial medulla neurons and their role in pain

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Chronic pain, defined as pain experienced in three out of a six month pre-interview period affects 17% of males and 20% of females in the Australian population. Opioid drugs such as morphine and codeine are the most effective drugs used to treat moderate to severe pain. However, the utility of these drugs is hampered by the development of a blunted response with repeated use. Furthermore, some clinically important pain states, particularly those caused by nerve injury, do not respond well to opioid drugs. Recent basic neurosceince research has identified groups of nerve cells deep within the brain that control sensitivity to pain as pain signals enter the spinal cord. Unfortunately in the presence of some chronic pain conditions, or chronic use of high doses of opioid drugs, these neurons undergo functional changes or adaptations that distort and increase the severity of pain sensation in a more or less permanent manner. This project uses electrical and chemical techniques to identify the basic physiology and pharmacology of single nerve cells in this brain region, so that their normal functions can be properly understood. We will then identify the cellular and molecular adaptations that occur in the nerve cells in animal models of chronic nerve injury and chronic morphine treatment to identify the nature of adaptations responsible for their aberrant function. We will then be in a position to rationally identify novel drug targets that can normalise the function of these nerve cells. This knowledge will provide potential targets for development of novel therapeutics to manage chronic pain.