BEHAVIORAL AND NEURAL CORRELATES OF PAIN AND ANALGESIA

疼痛是最常见但也很难处理的临床问题之一。 医生们所面对的。众所周知，疼痛是一种压力 经验。然而，疼痛的感知显然与非疼痛不同 伤害性压力源。这一建议接近于 啮齿动物的压力和伤害性感受：1)探索 给予伤害性刺激的神经元底物具有独特性 厌恶品质，2)确定应激如何调节神经元 对伤害性刺激的反应，以及3)与疼痛变化相关 麻醉药物引起的行为与中枢神经系统激活的变化 脊椎上水平，以确定特定的大脑区域可能 对麻醉剂负责。对伤害性反应的诱发改变。 我们建议通过关联行为变化来实现这些目标 不同类型伤害性和应激性刺激后的观察 以及由它们诱导的即刻早期基因(IEG)的表达模式 刺激物。这些模式将使用原位杂交进行定位。两者都有 伤害性和应激性刺激已被证明可以引起IEG的改变 在相关神经系统中的表达。然而，大多数人工作在伤害感受器 IEG的激活主要集中在脊髓。很少有研究检查过 这种反应的脊椎上成分，这项工作通常有 已经在麻醉的动物身上完成了。我们提出了一系列符合逻辑的 旨在回答以下问题的进展研究：1)做 伤害性和非伤害性应激源激活不同的神经元 系统？2)在慢性病期间，IEG激活模式发生了哪些变化 伤害性状态，以及医生长期接触伤害性感受器如何影响 对急性伤害性刺激的反应？3)应激史 动物对急性伤害性刺激改变神经元反应？4)什么是 麻醉药物对疼痛行为和脊髓上肌电活动的影响 什么时候在伤害性刺激之前或之后给药？我们希望这是 信息将提高对基本机制的理解 潜在的对疼痛的厌恶和情感反应，并可能导致 可以帮助减轻与疼痛相关的痛苦的治疗方法 天哪。

Pain is one of the most common, yet difficult to manage, clinical problems that physicians face. It is well known that pain is a stressful experience. However, pain clearly is perceived differently from non- nociceptive stressors. This proposal approaches the interface between stress and nociception in rodents with the following goals: 1) to explore the neuronal substrates that may give nociceptive stimuli their uniquely aversive qualities, 2) to determine how stress modulates neuronal responses to noxious stimulation, and 3) to correlate changes in pain behavior caused by narcotics with changes in neuronal activation at the supraspinal level, in order to identify specific brain areas that may be responsible for narcotic.induced alterations in response to nociception. We propose to accomplish these goals by correlating behavioral changes observed after different types of nociceptive and stressful stimulation with patterns of immediate early gene (IEG) expression induced by these stimuli. These patterns will be mapped using in situ hybridization. Both noxious and stressful stimuli have been shown to induce changes in IEG expression in relevant neuronal systems. However, most work in nociceptive IEG activation has focused on the spinal cord. Few studies have examined the supraspinal components of this response, and this work has typically been done in anesthetized animals. We propose a series of logically progressing studies designed to answer the following questions: 1) Do nociceptive and non-nociceptive stressors activate distinct neuronal systems? 2) What changes in IEG activation patterns occur during chronic nociceptive states, and how docs chronic exposure to nociceptors affect responses to acute nociceptive stimuli? 3) Does the stress history of an animal alter neuronal responses to acute nociceptive stimuli? 4) What are the effects of narcotics on pain behavior and supraspinal IEG activation when administered before or after nociceptive stimulation? We hope this information will improve the understanding of the basic mechanisms underlying aversive and affective responses to pain, and possibly lead to therapies that could help alleviate the suffering associated with pain in man.