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

慢性疼痛，定义为在六个月的访谈前三个月内经历的疼痛，影响了澳大利亚人口中17%的男性和20%的女性。吗啡和可待因等阿片类药物是用于治疗中度至重度疼痛的最有效药物。然而，这些药物的效用受到重复使用的迟钝反应的发展的阻碍。此外，一些临床上重要的疼痛状态，特别是由神经损伤引起的疼痛状态，对阿片类药物反应不佳。最近的基础神经科学研究已经确定了大脑深处的神经细胞群，当疼痛信号进入脊髓时，它们控制着对疼痛的敏感性。不幸的是，在一些慢性疼痛状况的存在下，或长期使用高剂量的阿片类药物，这些神经元经历功能变化或适应，以或多或少永久的方式扭曲和增加疼痛感觉的严重程度。该项目使用电学和化学技术来识别该脑区单个神经细胞的基本生理学和药理学，以便正确理解其正常功能。然后，我们将确定在慢性神经损伤和慢性吗啡治疗的动物模型中的神经细胞中发生的细胞和分子适应，以确定负责其异常功能的适应的性质。然后，我们将能够合理地确定新的药物靶点，使这些神经细胞的功能正常化。这些知识将为开发新的治疗方法来管理慢性疼痛提供潜在的靶点。

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.