Ethnic differences in effects of opioid blockade and behavioral analgesia on pain

描述(申请人提供)：持续性疼痛是一种公共卫生流行病，会产生巨大的经济成本和深刻的人类痛苦。大量证据表明，与非西班牙裔白人相比，非裔美国人经历严重、致残、临床疼痛状态(包括急性和慢性)的风险要高得多，而且对实验室研究中提供的各种有害刺激更敏感。虽然近年来在疼痛研究的许多领域取得了重大进展，但对疼痛反应中观察到的种族差异的解释仍然很少。鉴于美国人口的日益多样化，阐明疼痛感知的种族差异背后的机制已成为一个具有重大科学和临床重要性的话题，扩展这一研究路线最终将有助于缩小与疼痛相关的健康差异。因此，这项建议的目的是阐明内源性阿片系统在疼痛体验中的种族差异中所起的作用。具体地说，这个项目将调查对辣椒素诱导的疼痛的反应，认知-行为疼痛应对策略(即分心)产生的止痛效果，以及阻断内源性阿片系统是否会影响52名医学健康个体(非洲裔美国人50%，非西班牙裔白人50%，每个种族女性50%)在疼痛和止痛方面的种族差异。当前建议的目的是：1)评估内源性阿片类药物在辣椒素诱导的疼痛感知中的贡献的种族差异；2)表征非裔美国人和非西班牙裔白人在辣椒素诱导的疼痛期间牵张止痛有效性的差异；3)确定分心止痛任务的有效性的种族差异是否受到内源性阿片类药物的影响；以及4)心理因素是否影响疼痛敏感性、对行为止痛操作(分心)或阿片受体阻断的反应的种族差异。受试者将参加四次实验(以随机顺序)；在每一次实验中，他们都将单独或在分心任务中接触辣椒素，并将接受纳洛酮、阿片类拮抗剂或生理盐水的双盲给药。总之，这项拟议研究的结果将为疼痛感知的种族差异提供有价值的见解，并将提供迄今为止关于内源性阿片类药物对疼痛种族差异的贡献的最明确答案，确定导致疼痛体验种族差异的神经生物学途径，最终将提供干预目标，以减少非裔美国人疼痛的范围和影响。

DESCRIPTION (provided by applicant): Persistent pain is a public health epidemic producing enormous economic costs and profound human suffering. Considerable evidence indicates that, compared to non-Hispanic whites, African Americans are at substantially higher risk for experiencing severe, disabling, clinical pain states (both acute and chronic), and are more sensitive to a broad variety of noxious stimuli delivered in laboratory studies. While major advances in many areas of pain research have been made in recent years, explanations for the ethnic differences observed in responses to pain remain poorly understood. In light of the increasing diversity of the US population, illuminating the mechanisms that underlie ethnic differences in pain perception has become a topic of substantial scientific and clinical importance, and extending this line of research should eventually aid in reducing pain-related disparities in health. Therefore, the purpose of this proposal is to elucidate the role of the endogenous opioid system in contributing to ethnic differences in the experience of pain. Specifically, this project will investigate responses to capsaicin-induced pain, the analgesic effects produced by a cognitive-behavioral pain-coping strategy (i.e., distraction), and whether blockade of the endogenous opioid system affects ethnic differences in pain and analgesia in a sample of 52 medically healthy individuals (50% African American, 50% non-Hispanic White; 50% Women in each ethnic group). The aims of the current proposal are to: 1) evaluate ethnic differences in the contribution of endogenous opioids in pain perception of capsaicin induced pain; 2) characterize differences in the effectiveness of distraction analgesia during capsaicin-induced pain among African Americans and non-Hispanic whites; 3) determine whether ethnic differences in the effectiveness of a distraction analgesia task are influenced by endogenous opioids; and 4) whether psychological factors influence ethnic differences in pain sensitivity, response to the behavioral analgesic manipulation (distraction), or opioid receptor blockade. Subjects will participate in four experimental sessions (in a randomized order); in each of these they will be exposed to capsaicin "alone" or during a distraction task, and will undergo double-blinded administration of either naloxone, an opioid antagonist, or saline. Collectively, the findings from this proposed study will provide valuable insight into the mechanisms underlying ethnic differences in pain perception, and will provide the most definitive answer to date regarding the contribution of endogenous opioids to ethnic differences in pain, Identifying the neurobiological pathways that contribute to ethnic differences in the experience of pain will eventually provide targets for intervention to reduce the scope and impact of pain among African-Americans.