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

慢性疼痛的定义是六个月中有三个月在采访前经历的疼痛，在澳大利亚人口中，17%的男性和20%的女性受到影响。吗啡和可待因等阿片类药物是治疗中度至重度疼痛最有效的药物。然而，这些药物的用途因反复使用而产生迟钝的反应而受到阻碍。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发现，当疼痛信号进入脊髓时，大脑深处的神经细胞群控制着对疼痛的敏感性。不幸的是，在一些慢性疼痛的情况下，或者长期使用大剂量的阿片类药物，这些神经元经历了或多或少永久性的功能变化或适应，扭曲并增加了痛感的严重程度。该项目利用电气和化学技术来鉴定这一脑区单个神经细胞的基本生理和药理，以便正确理解它们的正常功能。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神经细胞中发生的细胞和分子适应，以确定导致其异常功能的适应的性质。然后，我们将能够合理地识别能够使这些神经细胞功能正常化的新药物靶点。这一知识将为开发治疗慢性疼痛的新疗法提供潜在的靶点。

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.