Prescribed opioid induced brain damage in chronic pain patients

处方阿片类药物引起慢性疼痛患者脑损伤

基本信息

批准号：
10216702
负责人：
Ignacio Badiola
金额：
$ 24.38万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10216702
关键词：
Acute Affect Amnesia Amnestic Disorder Animals Area Attenuated Basal Ganglia Behavior Bilateral Brain Brain Injuries Case Study Chronic Chronic low back pain Clinic Clinical Cognitive Cognitive deficits Data Dose Edema Electrodes Epidemic Epilepsy Exposure to Fentanyl Foundations Functional disorder Goals Hippocampus (Brain)Human Hypoxia Image Injury Intensive Care Ischemia Lead Limbic System Magnetic Resonance Imaging Mediating Medical Memory Memory Loss Neurocognitive Neuropsychological Tests Opiate Addiction Opioid Overdose Pain management Patients Perioperative Pharmaceutical Preparations Play Recording of previous events Regulation Reporting Reproducibility Research Risk Rodent Model Role Seizures Social Impacts Structure Testing Time Translating cell injury chronic pain chronic pain patient cognitive function diffusion weighted economic impact exposed human population follow-up high risk hippocampal atrophy illicit opioid memory process morphine equivalent neurocognitive test neuroimaging opioid abuse opioid overdose opioid therapy opioid use pain patient pre-clinical prescription opioid

项目摘要

The limbic system serves a number of critical functions, including regulation of behavior and memory. Perhaps no limbic structure plays a more critical role in memory processing than the hippocampus. The scientific foundation of the proposed research indicates that the hippocampus and association areas are at risk when exposed to opioids. Notably opioids often are used in large quantities, both acutely and chronically, and in many clinical contexts, leading to the current epidemic with opioid addiction, overdose, and reports of amnesia. Specific reports supporting the scientific foundations for the proposed research arise from: (1) Compelling reproducible data in animals and congruent observations in humans indicating that opioids activate the limbic system, producing hypermetabolism, acute cell injury, and memory loss with hippocampal atrophy. (2) Opioid-induced mesial hippocampal epileptiform activity with intracranial electrodes in epileptic humans. (3) Case reports of patients developing an amnestic syndrome in the setting of opioid overdose (OD) with complete diffusion-weighted hyperintensity and volume loss of both hippocampi on MRI. Notably, some reports describe OD patients without associated hypoxia, but with amnesia and MRI changes. (4) Chronic pain patients have been reported to develop cognitive deficits. It is currently unknown whether this is similar to that seen in patients presenting with opioid OD, the impetus for the proposed research. Our overall hypothesis is that patients with chronic pain who have been on long-term, high-dose opioids develop hippocampal injury and associated neurocognitive dysfunction. Therefore, we predict that these patients will have smaller hippocampal volumes and perform more poorly on neuropsychological tests of memory than matched chronic pain patients who do not use opioids. Using a combination of MRI imaging and neuropsychological testing, the specific aims of this proposal are to test the hypotheses in these patient groups that humans with chronic pain on long-term, high-dose opioids: 1. Will demonstrate smaller hippocampal volumes by MRI. 2. Will perform more poorly on neuropsychological tests of memory and associated hippocampal functions. If these high-risk but high-impact hypotheses are confirmed, thus translating ample preclinical observations, we will have revealed a previously unknown effect of opioid use on human cognitive function which could be relevant to millions of humans receiving prescription opioids, people with a history of opioid abuse, and patients who receive opioids perioperatively, peri-intensive care, or after injury. As such this would indicate a new discovery with potentially major medical, social, and economic impact.

边缘系统具有许多关键功能，包括行为和记忆的调节。也许没有哪个边缘结构比海马体在记忆处理中发挥着更重要的作用。拟议研究的科学基础表明，海马体和关联区是接触阿片类药物时面临风险。值得注意的是，阿片类药物经常被大量使用，无论是急性还是在许多临床情况下长期存在，导致当前阿片类药物成瘾、过量服用和失忆症的报告。支持拟议研究的科学基础的具体报告来自： (1) 令人信服的动物可重复数据和人类一致观察结果表明阿片类药物激活边缘系统，产生代谢亢进、急性细胞损伤和海马记忆丧失萎缩。 (2) 癫痫患者颅内电极阿片类药物诱导的内侧海马癫痫样活动。 (3) 因阿片类药物过量 (OD) 导致患者出现遗忘综合征的病例报告 MRI 上两个海马体的完全弥散加权高信号和体积损失。值得注意的是，一些报告描述 OD 患者没有相关的缺氧，但有健忘症和 MRI 变化。 (4) 据报道，慢性疼痛患者会出现认知缺陷。目前尚不清楚这是否与阿片类药物 OD 患者的情况相似，这也是本研究的动力。我们的总体假设是，长期服用大剂量阿片类药物的慢性疼痛患者发生海马损伤和相关的神经认知功能障碍。因此，我们预测这些患者的海马体积会更小，并且在神经心理学测试中表现更差记忆力优于不使用阿片类药物的慢性疼痛患者。结合使用 MRI 成像和神经心理学测试，该提案的具体目的是测试这些患者群体的假设长期服用高剂量阿片类药物而患有慢性疼痛的人： 1. 将通过 MRI 显示较小的海马体积。 2. 在记忆和相关神经心理学测试中表现更差海马体功能。如果这些高风险但高影响力的假设得到证实，从而转化大量的临床前观察结果，我们将揭示阿片类药物使用对人类认知功能的先前未知的影响，这可能是与数百万接受处方阿片类药物的人、有阿片类药物滥用史的人以及围手术期、围重症监护期或受伤后接受阿片类药物的患者。因此，这表明具有潜在重大医学、社会和经济影响的新发现。