Role of the Amygdala in Opioid Self-administration in Rats with Chronic Pain.

杏仁核在慢性疼痛大鼠阿片类药物自我给药中的作用。

基本信息

批准号：
7460617
负责人：
THOMAS JEFFREY MARTIN
金额：
$ 21.51万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-26 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7460617
关键词：
Acute Acute Pain Affect Amygdaloid structure Analgesics Animals Anterior Area Attenuated Behavior Blood Circulation Brain Brain region Chronic Control Animal Data Development Dose Fire - disasters Glutamates Heroin Hindlimb Hypersensitivity Intake Lead Left Mechanics Medial Medical Methadone Microdialysis Narcotic Antagonists Nerve Neurobiology Neurons Neurotransmitter Receptor Neurotransmitters Nociception Non-Malignant Nucleus Accumbens Opioid Opioid Receptor Pain Pain management Pathway interactions Patients Pharmaceutical Preparations Pharmacology Physical Dependence Physicians Property Psychological reinforcement Rattus Regulation Research Personnel Risk Role Self Administration Self-Administered Series Structure Testing Thalamic structure Time Ventral Tegmental Area Weight-Bearing state addiction beta-funaltrexamine chronic neuropathic pain chronic pain cingulate cortex drug seeking behavior in vivo injured mu opioid receptors nerve injury neurochemistry noradrenergic painful neuropathy prevent programs receptor research study therapy development transmission process

项目摘要

DESCRIPTION (provided by applicant): Opioid therapy for chronic nonmalignant pain is of concern to both patients and physicians regarding addiction and abuse liability. Acute therapy with opioid medications poses limited risks of physical dependence, addiction or problems with diversion of medications. The potential for these adverse consequences greatly increases with long term opioid therapy. Chronic non-malignant pain is a major use of long-term opioid therapy, and often requires relatively large doses of opioids compared to acute pain management. Although much is known about the neurobiology of opioid reinforcement in normal animals, relatively little is known about how chronic pain alters the abuse liability of opioids. Preliminary data indicate that pain from nerve injury selectively attenuates the abuse liability of opioids, and that tolerance to the pain relieving actions of opioids develops rapidly with continuous drug access through self-administration. Furthermore, the abuse liability of opioids is modulated to a much greater extent by manipulating opioid receptors in the amygdala in rats with neuropathic pain compared to normal animals, suggesting that the basic mechanisms responsible for opioid self-administration differ in the presence of chronic pain. Understanding the role of opioid receptors in the amygdala in modulating the abuse liability of opioids selectivley in animals in the presence of chronic pain could lead to therapies that minimize the risk of addiction in pain patients. Studies are proposed to determine how activation of opioid receptors during self-administration produces distinct actions in the amygdala of nerve-injured rats compared to control animals. Neurochemical and pharmacological studies are proposed to determine which neurotransmitters and neurotransmitter receptors are differentially activated during opioid self-administration in normal rats or rats with neuropathic pain. In a second series of studies, the changing role of the amygdala during the development of tolerance to the analgesic effects of opioids will be determined during self-administered dose escalation in normal and nerve-injured rats to determine how the development of tolerance influences the regulation of this brain structure and its' role in the development of addiction. A third series of experiments are proposed that involve manipulating opioid receptors in brain areas known to be involved in classical nociceptive (anterior cingulate cortex, medial thalamus, rostoventral medulla) or reinforcement (nucleus accumbens, ventral tegmental area) pathways to determine which brain regions are primarily responsible for drug-seeking behaviors in the presence or absence of pain in rats. These studies will hopefully define mechanisms that modulate drug-seeking behaviors in the presence of neuropathic pain, and identify potential candidates for therapies that minimize the risk of addiction and physical dependence in pain patients.

描述（由申请人提供）：患者和医生在成瘾和虐待责任方面都关注慢性非恶性疼痛的阿片类药物治疗。阿片类药物的急性治疗对身体依赖，成瘾或药物转移问题的风险有限。这些不良后果的潜力大大增加了阿片类药物治疗。慢性非恶性疼痛是长期阿片类药物疗法的主要用途，与急性疼痛管理相比，通常需要相对较大的阿片类药物。尽管对正常动物阿片类药物增强的神经生物学知之甚少，但对慢性疼痛如何改变阿片类药物的滥用责任的了解相对较少。初步数据表明，神经损伤的疼痛有选择地减弱阿片类药物的滥用责任，并且对阿片类药物的疼痛缓解作用的容忍性通过自我管理的连续药物进入而迅速发展。此外，与正常动物相比，通过操纵患有神经性疼痛的大鼠杏仁核中的阿片受体的阿片类受体的滥用责任在更大程度上受到调节，这表明导致阿片类药物自我导致的基本机制在慢性疼痛的存在下有所不同。了解阿片类受体在杏仁核中在慢性疼痛存在下选择阿片类药物在动物中的滥用责任中的作用，可能会导致疗法最大程度地减少疼痛患者成瘾的风险。提出了研究以确定自我给药过程中阿片受体的激活如何与对照动物相比，在神经损伤大鼠的杏仁核中产生不同的作用。提出了神经化学和药理研究，以确定在正常大鼠或神经性疼痛的正常大鼠或大鼠中，在阿片类药物自我给药期间，哪些神经递质和神经递质受体被差异化。在第二项研究中，将在正常和神经受损的大鼠自我管理剂量升级期间确定杏仁核在对阿片类药物的镇痛作用发展过程中的作用变化，以确定耐受性的发展如何影响这种大脑结构的调节及其在成瘾的发展中的作用。提出了第三组实验，该实验涉及在已知参与经典伤害感受器（前扣带回皮层，内侧丘脑，丘脑，rostoventral髓质）或增强型（核核，腹侧腹部，腹侧腹部）途径的大脑区域的疗法或对药物的疼痛行为的痛苦行为的措施或腹部的措施的行为是痛苦的行为。这些研究将有望定义在存在神经性疼痛的情况下调节寻求药物行为的机制，并确定潜在的候选疗法，以最大程度地减少疼痛患者的成瘾风险和身体依赖的风险。