Interactions Between the Brain Reward and Pain Systems.

大脑奖励和疼痛系统之间的相互作用。

• 批准号: 7562868
• 负责人: CONAN KORNETSKY
• 金额: $ 16.25万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562868
• 关键词: Analgesics; Animals; Area; Brain; Brain Part; Controlled Environment; Development; Electrodes; Environment; Environmental Risk Factor; Euphoria; Event; Food; Implant; Italy; Measurement; Methods; Modification; Morphine; Nociception; Opiate Addiction; Opiates; Outpatients; Pain; Pathway interactions; Perception; Peripheral; Persons; Pharmaceutical Preparations; Probability; Procedures; Rattus; Reporting; Research; Reticular Formation; Rewards; Risk; Role; Shock; Site; Spinal; System; Tail; War; Withdrawal; addiction; design; foot; heat stimulus; median forebrain bundle; pleasure; public health relevance; research study; sex; wound

DESCRIPTION (provided by applicant): The major objective of the proposed research is to study the interaction of the brain reward system with the brain pain system and the effects of morphine on this interaction. The intracerebral implanting of two stimulating electrodes, one in a reward site and one in a nociceptive site allows the determination of the brain stimulation escape threshold (BSE) in the presence of rewarding brain stimulation as well as the determination of the brain stimulation reward threshold (BSR) in the presence of nociceptive stimulation. This interaction should help us understand how events that produce pleasure may alter the perception of pain and the corollary, how events that cause pain may alter the perception of pleasure. A dramatic example of the environment causing an impact on the modulation of pain was the report of the WWII establishment of a beachhead at Anzio in Italy. Many of the wounded refused morphine (75%) and it was reported that many were euphoric. The wound meant they would be evacuated and thus escape alive from one of the highest casualty battles of the war. The brain stimulation reward procedure allows a direct activation of that area of the brain that subserves usual pleasurable events, e.g., food, sex, drugs and most likely euphoria. Measurement of the BSE threshold in the presence of rewarding brain stimulation allows a study of the direct effect of the brain reward centers on the perception of pain. The reciprocal question, does pain change the sensitivity of a brain reward site? Out-patients in pain, who are not in a controlled environment and are using prescription opiates, may be a greater risk for addiction than the person without pain exposed to the same opiates. Thus, the pain itself may increase the rewarding value of morphine facilitating opiate addiction. The specific experiments will be carried out in rats in which two electrodes are surgically implanted in each animal, one in a reward site (the medial forebrain bundle) and the other in a pain site (mesencephalic reticular formation). In addition to determining the effect of rewarding brain stimulation on the perception of pain caused by stimulating a brain pain pathway, experiments will be conducted on the effect of rewarding brain stimulation on two types of peripheral pain stimulation. These involve a reflexive tail withdrawal to a heat stimulus (spinal) and instrumental escape from nociceptive foot shock (supra spinal). In all of the experiments thresholds will be determined using a modification of the classic method of limits. PUBLIC HEALTH RELEVANCE: The proposed experiments are designed to determine if activation of those parts of the brain that are related to pleasure will alter the perception of pain and whether such activation will enhance the analgesic effects of morphine. A second aspect of the research will determine if the presence of pain contributes to the development of addiction by making the effect of morphine more pleasurable. It is possible that such findings will contribute to the development of better analgesics that are less addicting.

描述（由申请人提供）：拟议研究的主要目的是研究大脑奖励系统与脑疼痛系统的相互作用以及吗啡对这种相互作用的影响。脑内植入两个刺激的电极，一个在奖励部位中，一个在伤害感受部位中，可以在存在奖励大脑刺激的情况下确定大脑刺激逃脱阈值（BSE），以及在存在吸引感染力刺激的情况下大脑刺激奖励阈值（BSR）。这种互动应该有助于我们了解产生快乐的事件如何改变疼痛和推论的感知，导致疼痛的事件如何改变对愉悦感的看法。环境的一个戏剧性例子会影响疼痛的调节，这是第二次世界大战在意大利安齐奥建立海滩黑头的报告。许多受伤的人拒绝吗啡（75％），据报道许多人欣喜若狂。伤口意味着它们将被撤离，从而从战争的最高伤亡战之一中逃脱。大脑刺激奖励程序允许直接激活大脑的那个区域，从而使通常令人愉悦的事件，例如食物，性别，药物，最有可能的欣快感。在存在奖励大脑刺激的情况下，测量BSE阈值可以研究大脑奖励中心对疼痛感知的直接影响。相互的问题，疼痛会改变大脑奖励站点的敏感性吗？疼痛的门诊病人不在受控环境中并且使用处方鸦片的患者可能比没有暴露于同一阿片类药物的人更大的成瘾风险。因此，疼痛本身可能会增加吗啡促进鸦片成瘾的奖励价值。特定的实验将在大鼠中进行，其中两个电极在每只动物中植入两个电极，一个在奖励部位（内侧前脑束），另一个在疼痛部位（脑脑网状形成）中。除了确定奖励大脑刺激对刺激大脑疼痛途径引起的疼痛感知的影响外，还将进行实验，以奖励大脑刺激对两种类型的外周疼痛刺激的影响。这些涉及反身尾巴撤回热刺激（脊柱），并从伤害性脚冲击（Supra Spinal）中逃脱。在所有实验中，阈值将使用经典限制方法的修改确定。公共卫生相关性：拟议的实验旨在确定与愉悦相关的大脑部分的激活是否会改变对疼痛的看法，以及这种激活是否会增强吗啡的镇痛作用。研究的第二个方面将确定疼痛的存在是否通过使吗啡的作用更加愉悦而导致成瘾的发展。这种发现可能会有助于发展较少上瘾的更好的镇痛药。