Prescribed opioid induced brain damage in chronic pain patients

边缘系统具有许多重要功能，包括行为和记忆的调节。也许吧 在记忆处理过程中，没有哪个边缘结构比海马体更重要。 这项拟议研究的科学基础表明，海马体和关联区 在接触阿片类药物时有风险。值得注意的是，阿片类药物经常被大量使用，既有剧烈的，也有 在慢性和许多临床情况下，导致目前的阿片成瘾、过量服药和 有健忘症的报告。支持拟议研究的科学基础的具体报告来自： (1)在动物身上令人信服的重复性数据和在人类身上一致的观察表明阿片类药物 激活边缘系统，导致高代谢、急性细胞损伤和海马区记忆丧失 萎缩。 (2)阿片类药物诱发的癫痫人中脑海马癫痫样活动。 (3)患者在阿片类药物过量(OD)环境下出现遗忘症的病例报告 MRI表现为双侧海马区弥散加权全密度高信号及体积缩小。值得注意的是，一些 报道描述了没有相关缺氧，但有健忘症和MRI改变的OD患者。 (4)据报道，慢性疼痛患者会出现认知障碍。目前还不清楚这是不是 与出现阿片类药物过量的患者相似，这是拟议研究的动力。 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 出现海马区损伤和相关的神经认知功能障碍。因此，我们预测这些 患者的海马体体积会更小，在神经心理测试中的表现会更差 记忆力较匹配的不使用阿片类药物的慢性疼痛患者。结合使用MRI成像和 神经心理测试，这项建议的具体目的是在这些患者群体中测试假设 长期服用大剂量阿片类药物的慢性疼痛患者： 1.MRI显示海马区体积变小。 2.在记忆和相关的神经心理测试中会表现得更差 海马体功能。 如果这些高风险但高影响的假说得到证实，从而转化为大量的临床前观察， 我们将揭示一种以前未知的阿片类药物使用对人类认知功能的影响，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有关，以及 在围手术期、围重症监护期间或受伤后接受阿片类药物治疗的患者。因此，这将表明 具有潜在重大医疗、社会和经济影响的新发现。

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.