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

• 批准号: 8291425
• 负责人: JOHN J. A. MAROTA
• 金额: $ 49.82万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8291425
• 关键词: Address; Analgesics; Animals; Area; Behavior; Behavior assessment; Brain; Brain region; Chronic; Corpus striatum structure; Cues; DRD2 gene; Data; Dopamine; Dopamine D2 Receptor; Ethics; Extinction (Psychology); Freund' s Adjuvant; Functional Magnetic Resonance Imaging; Goals; Healthcare Systems; Human; Image; Injection of therapeutic agent; Investigation; Mediating; Methodology; Molecular; Morphine; Nucleus Accumbens; Opiate Addiction; Opiates; Opioid; Opioid Analgesics; Pain; Patients; Persistent pain; Persons; Pharmaceutical Preparations; Play; Population; Population Study; Process; Rattus; Research; Rewards; Rodent; Rodent Model; Role; Syndrome; System; Systems Biology; Testing; Translational Research; Ventral Tegmental Area; addiction; chronic pain; clinical practice; dopamine transporter; dopaminergic neuron; drug of abuse; human subject; inhibitor/antagonist; insight; mesolimbic system; neuroadaptation; neurotransmission; opioid abuse; pain behavior; patient population; preference; prescription drug abuse; receptor; research study; response; reuptake; success

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.

中脑边缘系统在调节疼痛和介导对阿片类药物的反应中起着关键作用。 这一点已在总体中心的一般描述中详细讨论。的这个系统 从腹侧被盖区（VTA）投射的多巴胺能神经元与奖赏有关 是成瘾过程中的焦点（Koob和Le Moal，2001年; Nestler，2004年; Escherow等人，2004; Nestler，2005; Spanagel和Heilig，2005）。此外，毒品的一个共同属性是， 滥用是NAc中多巴胺的释放。在这个系统中的适应被认为是一种机制， 成瘾多巴胺能系统的改变也被发现与疼痛状态有关 在动物和人类成像研究中（Borsook和Becerra，2006; Schweinhardt等人，2006年）。证据 Hagelberg最近综述了纹状体D2 DR在调节人类疼痛中的重要作用 等（Hagelberg等，2004年）。这种大脑区域和感受器系统的融合， 疼痛的调节和滥用药物的奖励作用表明了有待检验的中心假设 这个提议。