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

描述（由申请人提供）：持续性疼痛是一种公共卫生流行病，产生巨大的经济成本和深刻的人类痛苦。相当多的证据表明，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（急性和慢性）的风险显著更高，并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知之甚少。鉴于美国人口的多样性日益增加，阐明疼痛感知种族差异的机制已成为一个具有重大科学和临床意义的主题，扩展这一研究领域最终应有助于减少与疼痛相关的健康差异。因此，本提案的目的是阐明内源性阿片系统在促进疼痛体验的种族差异中的作用。具体来说，该项目将研究对辣椒素引起的疼痛的反应，认知行为疼痛应对策略（即，分心），以及内源性阿片系统的阻断是否会影响52名医学健康个体（50%非裔美国人，50%非西班牙裔白色;每个种族中50%女性）的疼痛和镇痛的种族差异。本提案的目的是：1）评价内源性阿片类药物在辣椒素诱导疼痛的疼痛感知中的作用的种族差异; 2）描述非裔美国人和非西班牙裔白人在辣椒素诱导疼痛期间分心镇痛有效性的差异; 3）确定分心镇痛任务有效性的种族差异是否受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、对行为镇痛操作（分心）的反应或阿片受体阻断的种族差异。受试者将参加四个实验阶段（以随机顺序）;在每个阶段中，他们将“单独”或在分心任务期间暴露于辣椒素，并将接受纳洛酮、阿片类拮抗剂或盐水的双盲给药。总的来说，这项拟议研究的结果将为疼痛感知的种族差异机制提供有价值的见解，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通路将最终为干预提供目标，以减少疼痛的范围和影响。非裔美国人的痛苦

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.