Functional Impact of Pain and Opioid Addiction on the Mesolimbic Dopaminergic Sys

疼痛和阿片类药物成瘾对中脑边缘多巴胺能系统的功能影响

基本信息

批准号：
7608893
负责人：
JOHN J. A. MAROTA
金额：
$ 29.1万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7608893
关键词：
Address Analgesics Animals Area Behavior Behavior assessment Brain Brain region Chronic Clinical Condition Corpus striatum structure Cues DRD2 gene Data Dopamine Dopamine D2 Receptor Extinction (Psychology)Freund&apos s Adjuvant Functional Magnetic Resonance Imaging Goals Healthcare Systems Human Image Injection of therapeutic agent Invasive Investigation Mediating Medical Methodology Molecular Morphine Nucleus Accumbens Opiate Addiction Opiates Opioid Opioid Analgesics Pain Patients Persistent pain Persons Pharmaceutical Preparations Play Population Population Study Process Purpose Rattus Research Rewards Rodent Rodent Model Role Score Syndrome System Systems Biology Testing Ventral Tegmental Area addiction chronic pain dopamine transporter dopaminergic neuron drug of abuse human study human subject inhibitor/antagonist insight mesolimbic system neuroadaptation neurotransmission opioid abuse preference prescription document prescription procedure receptor research study response reuptake success

项目摘要

The mesolimbic system plays a critical role both in modulating pain and mediating the response to opiates. This has been discussed in detail under General Description of the Overall Center. This system of dopaminergic neurons that project from the ventral tegmental area (VTA) has been implicated in the reward mechanism of opiates and is a focal point in the process of addiction (Koob and Le Moal, 2001; Nestler, 2004; Volkow et al., 2004; Nestler, 2005; Spanagel and Heilig, 2005). Moreover, a common attribute of drugs of abuse is the release of dopamine in NAc. Adaptations within this system are believed to be a mechanism of addiction. Alterations within the dopaminergic system also have been found to be associated with pain states in both animal and human imaging studies (Borsook and Becerra, 2006; Schweinhardt et al., 2006). Evidence for the important role of striatal D2DR in modulating pain in humans has been reviewed recently by Hagelberg et al. (Hagelberg et al., 2004). This convergence of brain regions and receptor system that impact upon both modulation of pain and the rewarding effects of drugs of abuse suggests the central hypothesis to be tested by this proposal.

中唇系统在调节疼痛和介导对阿片类药物的反应方面起着至关重要的作用。根据整个中心的一般描述，已经详细讨论了这一点。这个系统从腹侧盖区域（VTA）投射的多巴胺能神经元与奖励有关鸦片的机制，是成瘾过程中的焦点（Koob和Le Moal，2001； Nestler，2004; Volkow等，2004； Nestler，2005年； Spanagel和Heilig，2005年）。而且，药物的常见属性滥用是NAC中多巴胺的释放。据信该系统中的适应是一种机制瘾。还发现多巴胺能系统内的改变与疼痛状态有关在动物和人类成像研究中（Borsook和Becerra，2006； Schweinhardt等，2006）。证据对于纹状体D2DR在调节人类疼痛中的重要作用，Hagelberg最近审查了等。（Hagelberg等，2004）。大脑区域和受体系统的这种影响，影响这两者疼痛的调节和滥用药物的奖励作用表明，要测试的中心假设这个建议。