Ethnic differences in endogenous pain regulation: PET imaging of opioid receptors

内源性疼痛调节的种族差异：阿片受体的 PET 成像

• 批准号: 8775467
• 负责人: Claudia Michelle Campbell
• 金额: $ 40.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-10 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8775467
• 关键词: Accounting; Acute; Acute Pain; Adverse effects; Affect; African American; Age; Agonist; American; Analgesics; Binding; Brain; Brain region; Capsaicin; Cardiovascular system; Chronic; Clinical; Clinical effectiveness; Comorbidity; Data; Demographic Factors; Education; Employment; Ethnic Origin; Ethnic group; Exhibits; Future; Goals; Health; Image; Individual; Insula of Reil; Intervention; Investigation; Laboratories; Link; Marital Status; Measures; Mediating; Medical; Medicine; Metabolism; Neurobiology; Neurosecretory Systems; Neurotransmitters; Not Hispanic or Latino; Opiates; Opioid; Opioid Analgesics; Opioid Receptor; Opioid Receptor Binding; Pain; Pain management; Participant; Patients; Peripheral Nervous System; Pharmaceutical Preparations; Pharmacogenetics; Physical Sufferings; Physiological; Play; Population; Populations at Risk; Positron-Emission Tomography; Prevalence; Process; Psychophysiology; Public Health; Race; Regulation; Reporting; Research; Rest; Role; Sensory; Severities; Socioeconomic Status; Stimulus; System; Testing; Thalamic structure; Variant; Work; base; carfentanil; chronic pain; cost; disability; economic cost; endogenous opioids; ethnic difference; experience; health care service utilization; health disparity; illness length; improved; interest; mu opioid receptors; pain inhibition; public health relevance; racial difference; racial/ethnic difference; response; sex

DESCRIPTION (provided by applicant): Chronic pain is the number one motivator for healthcare utilization, affects over 100 million Americans, costs in excess of one trillion dollars annually and exacts profound suffering and physical disability. Considerable evidence has demonstrated that ethnic groups show substantial variability in the experience of acute and clinical pain, with African Americans (AAs) having increased prevalence of a number of clinical pain conditions and reporting higher levels of pain severity and pain-related disability in response to pain when compared to non-Hispanic whites (NHW). Evidence suggests that disparities between these groups are independent of other demographic factors such as age, sex, socioeconomic status, education, employment, marital status, and other potential confounders, such as medical comorbidities and disease duration. These ethnic differences have been mirrored in the laboratory where controlled, systematic noxious stimuli are applied to healthy individuals. Ethnic differences in laboratory pain responses are well-established, suggesting increased sensitivity to noxious stimulation among AAs compared to NHWs. In our previous work, we have demonstrated enhanced responsiveness in AAs to noxious stimulation on several tasks that indirectly assess endogenous pain-inhibitory systems that are at least partially opioid-mediated. Ethnic differences in endogenous opioid neurotransmitters in the central and peripheral nervous system suggest that these systems function less efficiently among AAs and may account for a substantial proportion of the ethnic differences observed in pain and analgesic responses. In addition, pharmacogenetic research shows substantial ethnic group differences in the metabolism, clinical effectiveness, and side-effect profiles of many drugs; including analgesics. The overwhelming majority of clinically used opioids elicit their effects through activation of the mu-opioid receptor, making it an extremely relevant target for investigation. We propose to examine ethnic differences in the supraspinal endogenous opioid system using positron emission tomography (PET) imaging of mu-opioid receptors employing the mu-selective agonist [11C] carfentanil. Healthy AAs and sex, age, SES matched, NHW participants will undergo one baseline (non-pain) and one capsaicin-induced pain PET session using [11C] carfentanil. The current proposal will measure mu-opioid binding potential and examine its role in ethnic group differences in pain sensitivity. Our overarching objective is to investigate the endogenous opioid system as the mechanism underlying the association between ethnicity and pain sensitivity, thereby enhancing our understanding of the neurobiology of ethnic differences. These findings will have far reaching implications; including elucidating a tangible, physiological mechanism underlying ethnic differences in pain, for prescribing analgesics and advancing personalized medicine. Enhancing our understanding of mechanisms underlying ethnic differences in pain is likely to assist in the refinement of targeted interventios to alleviate clinical pain in at-risk populations, and aid in reducing pain-related health disparites.

描述(申请人提供)：慢性疼痛是医疗保健利用的头号动机，影响着超过1亿美国人，花费超过1万亿美元 每年都会造成严重的痛苦和身体残疾。大量证据表明，族裔群体在急性和临床疼痛的经历上表现出很大的差异性，与非西班牙裔白人相比，非洲裔美国人(非裔美国人)的一些临床疼痛状况的患病率增加，报告的疼痛严重程度和疼痛相关残疾程度更高。有证据表明，这些群体之间的差异与其他人口统计因素无关，如年龄、性别、社会经济地位、教育、就业、婚姻状况，以及其他潜在的混杂因素，如医疗合并症和病程。这些种族差异在实验室中得到了反映，在实验室里，对健康的人施加了受控的、系统的有害刺激。实验室疼痛反应的种族差异是公认的，这表明与NHW相比，AAS对伤害性刺激的敏感性更高。在我们以前的工作中，我们已经在间接评估至少部分由阿片类药物介导的内源性疼痛抑制系统的几个任务中展示了AAS对有害刺激的增强反应性。中枢和外周神经系统内源性阿片类神经递质的种族差异表明，这些系统在再生障碍性贫血中的运作效率较低，可能是疼痛和止痛反应中观察到的种族差异的主要原因。此外，药物遗传学研究表明，包括镇痛剂在内的许多药物在新陈代谢、临床疗效和副作用方面存在显著的种族差异。绝大多数临床使用的阿片类药物是通过激活u-阿片受体而产生作用的，这使其成为一个极其相关的研究目标。我们建议使用Mu选择性激动剂[11C]卡芬太尼对Mu阿片受体进行正电子发射断层扫描(PET)成像，以检查脊柱上内源性阿片系统的种族差异。健康的AAS与性别、年龄、SES匹配，NHW参与者将接受一次基线(无疼痛)和一次辣椒素诱导的疼痛PET治疗，使用[11C]卡芬太尼。目前的提案将测量Mu-阿片类药物结合潜力，并检查其在种族群体疼痛敏感性差异中的作用。我们的总体目标是研究内源性阿片系统作为种族和疼痛敏感性之间联系的潜在机制，从而加强我们对种族差异的神经生物学的理解。这些发现将具有深远的影响；包括阐明疼痛种族差异背后的有形生理机制，用于开止痛药和推进个性化药物。加强我们对疼痛种族差异的机制的理解，可能有助于完善有针对性的干预措施，以减轻高危人群的临床疼痛，并有助于减少与疼痛相关的健康差异。