Synaptic environment of nociceptive inputs to the spinal cord

脊髓伤害性输入的突触环境

• 批准号: nhmrc : 426750
• 负责人: Prof Ian Gibbins
• 金额: $ 33.33万
• 依托单位: Flinders University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/synaptic-environment-nociceptive-spinal-cord/81197
• 关键词: Synaptic; environment; nociceptive; inputs; spinal

Pain affects everyone at some stage in their life. Usually, the pain subsides by itself as the underlying cause is resolved. Thus, the damaged tissue heals or we move away from a potentially injurious stimulus and we become free of pain. However, pain can persist for two main reasons: the underlying cause cannot be treated adequately and the painful stimulus continues; or the pain is maintained long after the primary stimulus has resolved. This ongoing pain often is resistant to alleviation by common analgesics. Therefore, a major aim of the pharmaceutical industry is the development of new drugs to target persistent pain. This requires a thorough understanding of how the nerves that detect painful stimuli transmit that information into the spinal cord, and then on to the brain, where we construct a conscious perception of the pain. Various kinds of painful stimuli, such as tissue damage, noxious chemicals, or extreme temperatures, are detected by different types of nerves. Each nerve type can be identified by its characteristic chemical profile. Recently, we found that some of these nerves probably do not transmit their messages to the spinal cord in the way everyone had thought. This means that there must be an alternative way for many types of painful stimuli to be transmitted into the spinal cord. In this project, we will use a sophisticated suite of modern microscopic and electrical recording techniques to find out what this alternative mechanism is. Our central idea is that most types of painful stimuli simultaneously activate two types of sensory nerves. These nerves then connect with specific nerve cells in the spinal cord before painful information is relayed to the brain. Our proposal suggests a new mechanism for understanding how pain can develop from being an acute defensive reaction to a chronic problem. In turn, this should lead to improved strategies for developing and testing new analgesic drugs.

疼痛会影响每个人在他们生命中的某个阶段。通常，疼痛会随着根本原因的解决而自行消退。因此，受损的组织愈合或我们远离潜在的有害刺激，我们变得没有疼痛。然而，疼痛可能持续存在有两个主要原因：根本原因无法得到充分治疗，疼痛刺激仍在继续;或者在主要刺激解决后疼痛仍持续很长时间。这种持续的疼痛通常对普通止痛药的缓解有抵抗力。因此，制药行业的一个主要目标是开发针对持续性疼痛的新药。这就需要彻底了解检测疼痛刺激的神经如何将信息传递到脊髓，然后传递到大脑，在那里我们构建了对疼痛的有意识感知。各种疼痛刺激，如组织损伤，有毒化学物质或极端温度，由不同类型的神经检测。每种神经类型都可以通过其特有的化学特征来识别。最近，我们发现这些神经中的一些可能并不像大家想象的那样将信息传递到脊髓。这意味着，必须有一种替代的方式将许多类型的疼痛刺激传递到脊髓。在这个项目中，我们将使用一套先进的现代显微镜和电子记录技术来找出这种替代机制是什么。我们的中心思想是，大多数类型的疼痛刺激同时激活两种类型的感觉神经。然后，这些神经在疼痛信息传递到大脑之前与脊髓中的特定神经细胞连接。我们的建议提出了一种新的机制，以了解疼痛如何从急性防御反应发展为慢性问题。反过来，这将导致开发和测试新止痛药的改进策略。