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

项目概要/摘要 建议的补充利用了母U 01项目（1U 01 HL 150568 -01; PI： Michael T. Smith，PhD）来检查慢波睡眠[（SWS）;即，NREM阶段3睡眠]， 种族相关的压力，和静息状态功能性脑连接（rsFC）实验疼痛敏感性， 居住在美国的健康的非西班牙裔黑人和非西班牙裔白色成年人（US-NHB和US-NHW， 分别）。US-NHB成年人经历慢性疼痛的几率高出1.8倍， 与US-NHW同行相比，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- 相关压力是美国NHB人群中与不良疼痛结局相关的既定健康决定因素 个体虽然以前的研究表明，种族主义增加非稳态负荷负担-或生理 由于慢性压力的干扰-不成比例地影响US-NHB个体的健康， 种族主义/种族相关的压力影响疼痛的慢性化和敏感性没有完全确定。 在个体水平上理解这种机制可以促进US-NHB个体的公平疼痛护理 通过新的预防和治疗形式，补充提供者的教育和政策努力， 系统性种族主义SWS的特征是交感神经系统活动减少， 调节非稳态负荷。以前的工作表明，US-NHB个体的SWS明显减少 与US-NHW个体相比，SWS减少与种族相关的压力有关。降低SWS通常 在慢性疼痛的病例对照研究中观察到，并且与以下背景下的疼痛敏感性升高有关： 正常的睡眠时间结合起来，这些发现表明，减少SWS可能作为一种机制， 种族相关的压力会影响US-NHB个体的疼痛过程;然而，这一假设尚未被证实。 在以前的工作中探索。控制心理社会因素，本项目有3个目标：[1]确定 SWS是否介导了实验性疼痛敏感性的种族差异，[2]询问这种关联 种族相关的压力和奖励系统的rsFC之间的关系-一个与疼痛慢性化相关的大脑网络 风险和负面影响减少SWS，并[3]检查是否奖励系统rsFC缓和 SWS-疼痛协会。沿着这些研究工作，候选人将完成教学法，并获得 迈克尔·史密斯博士--睡眠疼痛二分体的主要专家--和克劳迪娅·坎贝尔博士--的指导 民族疼痛差异方面的国家专家-在以下领域：[1]睡眠-疼痛二元体，[2]机制 种族间疼痛差异，[3]先进的神经成像技术，[4]文化响应的指导。 这些专业和项目数据将帮助候选人启动一个独立的研究计划， 疼痛治疗反应的机制-特别是与种族差异有关-并允许她 有效地指导来自学术界历来代表性不足的群体的学员。

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.