VARIOUS PAIN STATES ON OPIOID TRANSPORT ACROSS THE BBB

阿片类药物跨血脑屏障转运的各种疼痛状态

• 批准号: 6378475
• 负责人: JASON D HUBER
• 金额: $ 4.02万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6378475
• 关键词: biological transport; blood brain barrier; brain metabolism; chronic pain; endogenous opioid; laboratory rat; pain; peptides; protein transport

DESCRIPTION: (Applicant's Abstract) Chronic pain affects nearly 70 million people a year in the United States and costs billions of dollars in medical treatments and lost productivity. To date, all investigations concerning the blood-brain barrier and opioid entry into the brain have been performed on naive, non-pained rats. The focus of my research will be to build upon already existing and proven research methodologies by introducing a pathological state (i.e. chronic pain) and then examining opioid peptide delivery across the BBB as well as determine what other BBB mechanisms are altered during pain. This study will be the first of its kind to examine the role that BBB plays in opioid transport and distribution during pain. A superior model to those used previously in assessing opioid delivery to the brain, since opioid analgesics are typically administered in an effort to relieve pain. The hypothesis of this study is that mediators released during pain affect the biochemical and molecular structure of the blood-brain barrier, resulting in alterations of opioid peptide transport into the brain. These studies will provide new information about mechanisms that may contribute to the permeability changes observed during chronic pain states. Ultimately, this grant may identify a pharmacological approach that could be used in conjunction with current therapies to alleviate pain with greater efficacy and fewer adverse side effects.

描述：（申请人摘要） 在美国，慢性疼痛每年影响近7000万人， 花费了数十亿美元的医疗费用和生产力的损失。到目前为止， 所有关于血脑屏障和阿片类药物进入 已经在未处理的、无疼痛的大鼠上进行了脑损伤的研究。我研究的重点是 将在现有的和经过验证的研究方法的基础上， 引入病理状态（即慢性疼痛），然后检查阿片类药物 肽通过血脑屏障的传递以及确定其他血脑屏障机制 在疼痛时会发生变化这项研究将是同类研究中的第一个 BBB在疼痛过程中阿片类物质转运和分布中的作用。一 上级模型，优于先前用于评估阿片类药物递送至 大脑，因为阿片类镇痛药通常是为了 减轻疼痛。这项研究的假设是， 疼痛影响血脑屏障的生物化学和分子结构， 导致阿片肽转运入脑的改变。这些 研究将提供有关可能有助于 在慢性疼痛状态期间观察到的渗透性变化。最终这 格兰特可以确定一种药理学方法， 与目前的治疗，以减轻疼痛，更大的疗效和更少的 不良副作用