Mechanisms of opioid receptor desensitisation in single neurons

包括吗啡和可待因在内的阿片类药物是已知最有效的镇痛药，但它们的效用受到耐受性（需要增加药物剂量才能达到同样的效果）、身体依赖（以停止使用时的衰弱性戒断综合征为特征）以及成瘾或强迫性药物寻求和使用等问题的限制。更好地了解这些不良过程背后的机制可能会导致开发出更容易接受的止痛剂。该项目将增加对神经细胞中发生的初始分子事件的理解，这些事件被认为是阿片类药物耐受性和身体依赖发展的基础。这些研究将集中在从动物身上分离和培养的感觉神经细胞上，这是止痛药物的主要靶点之一。了解这些过程将有助于制定更好的策略，以避免产生耐受性和身体依赖性。他们还将在分子水平上确定决定为什么一种阿片类药物比另一种药物产生更大耐受性的机制。这一知识可能会导致疼痛缓解药物的发展，这些药物在慢性疼痛的管理中不会轻易失去其有效性。

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.