Effects of experimental sleep disruption and fragmentation on cerebral Mu-opioid receptor function, Mu-opioid receptor agonist analgesia, and abuse liability.

项目摘要/摘要 拟议的补充方案利用了上级U01项目的基础设施(1U01HL150568-01；PI： Michael T.Smith博士)研究慢波睡眠的作用[(SWS)；即NREM阶段3睡眠]， 种族相关应激和静息状态脑功能连接(RsFC)对实验性疼痛敏感性的影响 居住在美国的健康的非西班牙裔黑人和非西班牙裔白人成年人(US-NHB和US-NHW， )。美国-NHB成年人经历慢性疼痛的几率高出1.8%，并报告说 与US-NHW同龄人相比，临床疼痛强度和疼痛相关残疾更大。种族主义和由此产生的种族- 相关压力是已确定的与US-NHB中不良疼痛结局相关的健康决定因素 个人。尽管先前的研究表明种族主义会增加平衡负荷--或生理性负荷 慢性压力引起的扰动--不成比例地影响美国-NHB患者的健康，其机制 种族主义/种族相关的压力对疼痛、时代化和敏感性的影响尚未完全确定。 在个人层面上了解这种机制可以促进美国-NHB患者的公平疼痛护理 通过新的预防和治疗形式补充提供者的教育和政策努力，以消除 系统性种族主义。SWS的特征是交感神经系统活动减少，并严重下降 调节不平衡负荷。之前的研究表明，美国-NHB人群的SWS明显减少 与美国nhw人相比，SWS减少与种族相关的压力有关。SWS降低的情况经常 在慢性疼痛的病例对照研究中观察到，在以下情况下与疼痛敏感度升高有关 正常的总睡眠时间。总而言之，这些发现表明，减少的SWS可能是一种机制，通过 哪些种族相关的压力会影响美国-NHB人群的疼痛过程；然而，这一假设尚未得到证实 在以前的工作中进行了探索。控制心理社会因素，本项目有三个目标：[1]确定 SWS是否调节实验性疼痛敏感性的耳鼻孔差异，[2]询问两者之间的联系 种族相关的压力和奖励系统的rsfc之间--一个与疼痛时序化有关的大脑网络 风险，并受到减少的SWS的不利影响，以及[3]检查奖励制度rsFC是否调节 SWS-疼痛协会。随着这些研究的努力，候选人将完成教学并收到 迈克尔·史密斯博士和克劳迪娅·坎贝尔博士的指导-睡眠疼痛二元组的领先专家 在以下领域研究耳鼻咽喉疼痛差异的国家专家：[1]睡眠-疼痛二元体，[2]机制 [3]先进的神经成像技术，以及[4]对文化反应的指导。 这些熟练程度和项目数据将帮助候选人启动一项独立的研究计划 疼痛治疗反应的机制--特别是与鼻-鼻差异有关--并允许她 有效地指导来自学术界历史上代表性不足的受训人员。

PROJECT SUMMARY/ABSTRACT The proposed supplement leverages the infrastructure of a parent U01 project (1U01HL150568-01; PI: Michael T. Smith, PhD) to examine the contributions of slow wave sleep [(SWS); i.e., NREM Stage 3 sleep], race-related stress, and resting-state functional brain connectivity (rsFC) to experimental pain sensitivity in healthy non-Hispanic Black and non-Hispanic White adults residing in the US (US-NHB and US-NHW, respectively). US-NHB adults have up to 1.8 greater odds of experiencing chronic pain and report significantly greater clinical pain intensity and pain-related disability compared to US-NHW peers. Racism and resultant race- related stress are established health determinants associated with adverse pain outcomes among US-NHB individuals. Although previous work shows that racism increases allostatic load burden – or physiological perturbations due to chronic stress – to disproportionately impact US-NHB individuals' health, the mechanisms by which racism/race-related stress impacts pain chronification and sensitivity are not fully established. Understanding such mechanisms at the individual level can promote equitable pain care for US-NHB individuals via novel forms of prevention and treatment that complement provider education and policy efforts to eliminate systemic racism. SWS is characterized by reductions in sympathetic nervous system activity and critically down regulates allostatic load burden. Previous work has shown stark SWS reductions among US-NHB individuals compared to US-NHW individuals, and reduced SWS is linked to race-related stress. Reduced SWS is frequently observed in case-control studies of chronic pain and is linked with heightened pain sensitivity in the context of normal total sleep duration. Combined, these findings suggest that reduced SWS might act as a mechanism by which race-related stress impacts pain processes in US-NHB individuals; yet, this hypothesis has not been explored in previous work. Controlling for psychosocial factors, the present project has 3 aims: [1] determine whether SWS mediates ethnoracial differences in experimental pain sensitivity, [2] interrogate the association between race-related stress and rsFC of the reward system – a brain network associated with pain chronification risk and adversely impacted by reduced SWS, and [3] examine whether reward system rsFC moderates the SWS-pain association. Along with these research efforts, the candidate will complete didactics and receive mentorship by Dr. Michael Smith – a leading expert in the sleep-pain dyad – and Dr. Claudia Campbell – a national expert in ethnoracial pain disparities – in the following areas: [1] the sleep-pain dyad, [2] mechanisms of ethnoracial pain disparities, [3] advanced neuroimaging techniques, and [4] culturally responsive mentorship. These proficiencies and project data will help the candidate launch an independent research program examining mechanisms of pain treatment responses – particularly related to ethnoracial disparities – and allow her to effectively mentor trainees from historically underrepresented groups in academia.