Synergism between opioids and other agents at central primary afferent synapses

阿片类药物和其他药物在中枢初级传入突触处的协同作用

• 批准号: nhmrc : 107489
• 负责人: Prof Macdonald Christie
• 金额: $ 13.52万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/synergism-opioids-agents-afferent-synapses/76843
• 关键词: Synergism; between; opioids; other; agents

Opioids, such as codeine, pethidine and morphine, are the most effective pain relieving drugs known but their clinical utility is limited by hazardous and potentially lethal side effects, as well as the development of tolerance and physical dependence with associated addiction liability. Recent research in our laboratory has identified for the first time a mechanism in the mammalian brain by which the pain relieving actions of opioids can be greatly enhanced by drugs that independently modulate biochemical processes distinct from those altered by opioids. Exploitation of these mechanisms has great potential for the development of new pharmacotherapies for effective pain relief with minimised side effects. These synergistic mechanisms appear to be at least as important for pain relief in the spinal cord as in brain, so the proposed studies will first examine the basis for synergism with opioid mediated pain relief in spinal cord. There is also strong evidence that the mechanisms to be studied in the proposed work are pivotal in the development of debilitating, chronic pain conditions that involve heightened sensitivity to painful stimuli and-or painful responses to normally innocuous stimuli such as light touch. Such aberrant responses can persist long after initial tissue damage has recovered. It is known that opioids can limit somewhat the initial steps in the induction of these abnormal responses but the mechanisms involved are unknown. The proposed studies will contribute to resolution of these mechanisms. Better understanding of the basis of these pathological processes will lead to better strategies for retarding or preventing the development of chronic pain conditions.

阿片类药物，如可待因、哌替啶和吗啡，是已知最有效的止痛药物，但其临床用途受到危险和潜在致命副作用以及与相关成瘾倾向相关的耐受性和身体依赖性的限制。我们实验室最近的研究首次确定了哺乳动物大脑中的一种机制，通过这种机制，通过独立调节与阿片类药物改变的生化过程不同的药物，可以大大增强阿片类药物的镇痛作用。利用这些机制对于开发新的药物疗法具有巨大的潜力，可以有效缓解疼痛并最大限度地减少副作用。这些协同机制似乎对于缓解脊髓疼痛至少与大脑一样重要，因此拟议的研究将首先检查与阿片类药物介导的脊髓疼痛缓解协同作用的基础。还有强有力的证据表明，拟议工作中要研究的机制对于使人衰弱的慢性疼痛病症的发展至关重要，这些病症涉及对疼痛刺激的高度敏感性和/或对通常无害的刺激（例如轻触）的疼痛反应。在最初的组织损伤恢复后，这种异常反应可能会持续很长时间。众所周知，阿片类药物可以在一定程度上限制诱导这些异常反应的初始步骤，但所涉及的机制尚不清楚。拟议的研究将有助于解决这些机制。更好地了解这些病理过程的基础将有助于制定更好的策略来延缓或预防慢性疼痛的发展。