Neuroimaging of CNS Interactions in Addiction, Chronic Pain and Analgesia

成瘾、慢性疼痛和镇痛中中枢神经系统相互作用的神经影像学

• 批准号: 7762436
• 负责人: Pamela Elizabeth Meredith
• 金额: $ 12.6万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762436
• 关键词: Absence of pain sensation; Abstinence; Amygdaloid structure; Analgesics; Animals; Anxiety; Basal Ganglia; Behavior; Brain; Brain region; Cell Nucleus; Cerebrovascular Circulation; Chronic; Cocaine; Cognitive; Cognitive deficits; Control Animal; Coupled; Development; Disease; Dopamine; Dopamine Receptor; Drug Addiction; Drug Controls; Drug usage; Exhibits; Exposure to; Family; Formalin; Functional Magnetic Resonance Imaging; Glucose; Human; Hypothalamic structure; Injection of therapeutic agent; Lead; Learning; Limbic System; Memory; Methods; Modeling; Morphine; Names; Neurons; Nociception; Opioid; Opioid Receptor Binding; Pain; Pattern; Peripheral nerve injury; Pharmaceutical Preparations; Predisposition; Process; Productivity; Property; Recording of previous events; Relative (related person); Self Administration; Self-Administered; Signal Transduction; Societies; Stimulus; Stress; Structure; System; Techniques; addiction; awake; chronic pain; cingulate cortex; cocaine exposure; constriction; dopamine system; drug addict; experience; frontal lobe; insight; mesolimbic system; midbrain central gray substance; nerve injury; neural circuit; neuroimaging; neuromechanism; painful neuropathy; psychostimulant; public health relevance; receptor; receptor binding; response; social

DESCRIPTION (provided by applicant): Repeated exposure to cocaine produces persistent adaptations in the brain resulting in an enhanced response to subsequent exposure to psychostimulants, opioids or stress. These include altered supraspinal activation patterns in numerous brain regions. For example, relative to controls, long-term cocaine abusers exhibit lower regional cerebral blood flow (rCBF), glucose utilization, and fMRI bold signaling in limbic regions such as the basal ganglia and frontal cortex and these alterations persist even after long periods of abstinence. However, it is not clear whether these differences in functional activation in the brain are a consequence of drug use or precede drug use and may underly a predisposition to drug addiction (DA). Noxious stimulation also increases neuronal activity in limbic regions and these effects are modulated by opioids in humans. In animals, neuroimaging studies have identified activation of similar brain regions following formalin injection or chronic constriction nerve injury (CCI). For example, twelve weeks following CCI, animals in chronic pain (CP) show a progressive increase in activation in multiple limbic regions, including the cingulate cortex, amygdala, periaqueductal grey and hypothalamic nuclei and limbic regions identified in DA. Unfortunately, no study has looked specifically for overlapping neural circuits in both DA and CP animals. Accordingly, we propose to identify the shared and unique supraspinal mechanisms involved in DA and CP animals and evaluate the effect of an analgesic treatment on these brain systems. First, we will characterize cognitive behaviors in DA and CP animals, coupled with (1) a neuroimaging technique for assessing localized changes in cerebral blood flow in an awake, freely moving animal and (2) receptor autoradioaugraphy to identify changes in dopamine and opioid receptor binding. Second, we will determine the effect of morphine administration on these systems. Specifically, we will identify changes in the activation within limbic regions involved in drug addiction and nociceptive processing. Results from this study will provide important insights into the CNS consequences and neural mechanisms of drug addiction and chronic pain that will lead to the development of new therapies for better management and treatment. PUBLIC HEALTH RELEVANCE: Drug addiction and chronic pain represent two major problems for our society. Both lead to loss of worker productivity and destruction of family and social ties, to name a few. Results from this study will provide important insights into the CNS consequences and neural mechanisms of drug addiction and chronic pain that will lead to the development of new therapies for better management and treatment of these disorders.

描述（由申请人提供）：反复接触可卡因会在大脑中产生持续的适应，从而增强对随后暴露于心理刺激剂，阿片类药物或压力的反应。这些包括众多大脑区域的上脊髓激活模式改变。例如，相对于对照组，长期可卡因施肥者表现出较低的区域脑血流（RCBF），葡萄糖利用率和fMRI大胆的信号在基础神经节和额叶皮层等边缘区域，即使经过长时间的持久，这些变化仍然存在。但是，尚不清楚大脑功能激活的这些差异是药物使用还是在药物使用之前的结果，并且可能是对药物成瘾的倾向（DA）。有害刺激还增加了边缘区域的神经元活性，这些作用受到人类阿片类药物的调节。在动物中，神经影像学研究确定了福尔马林注射或慢性狭窄神经损伤（CCI）后相似的大脑区域的激活。例如，在CCI后十二周，慢性疼痛（CP）的动物显示多个边缘区域的激活逐渐增加，包括扣带回皮质，杏仁核，杏仁核，灰灰色和下丘脑核和下丘脑核和下丘脑区域。不幸的是，没有研究专门研究DA和CP动物中的神经回路。因此，我们建议确定DA和CP动物涉及的共享和独特的上脊髓机制，并评估镇痛治疗对这些大脑系统的影响。首先，我们将表征DA和CP动物中的认知行为，再加上（1）一种神经影像学技术，用于评估清醒，自由移动动物的脑血流的局部变化，以及（2）受体自动载体，以识别多巴胺和阿片类受体结合的变化。其次，我们将确定吗啡给药对这些系统的影响。具体而言，我们将确定与药物成瘾和伤害性处理有关的边缘区域内激活的变化。这项研究的结果将提供对中枢神经系统成瘾和慢性疼痛的后果和神经机制的重要见解，这将导致开发新的疗法，以更好地管理和治疗。 公共卫生相关性：吸毒成瘾和慢性疼痛是我们社会的两个主要问题。两者都导致工人生产力的丧失以及对家庭和社会联系的破坏，仅举几例。这项研究的结果将提供有关药物成瘾和慢性疼痛的中枢神经系统后果和神经机制的重要见解，这将导致新疗法的发展，以更好地管理和治疗这些疾病。