Pain in PASC - The Role of Sleep Disturbances

PROJECT SUMMARY Up to 80% of individuals infected with SARS-CoV-2 continue to experience persistent and debilitating symptoms that extend >3 months into the post infection period, also called post-acute SARS-CoV-2 sequela (PASC) or 'long COVID'. Pain is among the most common symptoms remaining after 6 months following the initial infection, along with sleep disturbance, fatigue, and cognitive impairment. The high prevalence rates of post-viral complications are alarming. There is an urgent need to understand the disease mechanisms and identify therapeutic targets. To date, factors such as the severity of the initial infection, medical co- morbidities, or age do not sufficiently explain who develops PASC and who does not. We hypothesize that sleep disturbance is a critical factor in the development and non-resolution of pain in PASC. Current research strongly indicates that sleep supports maintenance of a pain-free state and optimal functioning of central pain processing pathways. The proposed work will be the first to characterize the inter-relationship between sleep disturbance and pain in PASC patients. Twenty patients with PASC (PCR confirmed diagnosis of SARS-CoV-2), and 10 who had PCR confirmed infection but did not develop PASC (PASC+ and PASC-), will be included in this research (>18 years of age, 50% females). A comprehensive pain testing and sleep assessment approach consisting of at-home and in- laboratory subjective and objective monitoring methodologies will be used to address the following aims: Aim 1 will characterize pain in PASC+ compared with PASC-. We will (a) monitor day-to-day spontaneous/ongoing pain in the at-home environment, and (b) assess somatosensory deficits using quantitative somatosensory testing (QST) during the in-hospital Clinical Research Center (CRC) visit. We will evaluate the functional status of somatosensory modalities of touch, warmth, pressure, heat, and cold, as well as the capacity of the central nervous system (CNS) to modulate pain. Aim 2: will address the strength of association and directionality between indicators of sleep disturbance and spontaneous pain/somatosensory functioning in PASC. Indicators of sleep disturbances will be assessed by (a) day-to-day diary- and actigraphy-based monitoring of sleep in the at-home environment, and (b) polysomnography (PSG) in the in-hospital environment to evaluate macro- and microstructural sleep characteristics. The proposed work will be the first study to explore the role of sleep disturbance in the persistence and non-resolution of pain in PASC. Knowledge gained has the potential to influence therapeutic strategies aimed at normalizing pain in PASC, including addressing sleep difficulties as a first intervention to prevent the development of chronic pain in this patient population.