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

项目总结/文摘

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.