Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

Abstract

Chronic pain and sleep disturbance are highly comorbid disorders, which leads to barriers to treatment and significant healthcare costs. Understanding the underlying genetic and neural mechanisms of the interplay between sleep disturbance and chronic pain is likely to lead to better treatment. In this study, we combined 1206 participants with phenotype data, resting-state functional magnetic resonance imaging (rfMRI) data and genotype data from the Human Connectome Project and two large sample size genome-wide association studies (GWASs) summary data from published studies to identify the genetic and neural bases for the association between pain and sleep disturbance. Pittsburgh sleep quality index (PSQI) score was used for sleep disturbance, pain intensity was measured by Pain Intensity Survey. The result showed chronic pain was significantly correlated with sleep disturbance (r = 0.171, p-value < 0.001). Their genetic correlation was r g = 0.598 using linkage disequilibrium (LD) score regression analysis. Polygenic score (PGS) association analysis showed PGS of chronic pain was significantly associated with sleep and vice versa. Nine shared functional connectivity (FCs) were identified involving prefrontal cortex, temporal cortex, precentral/ postcentral cortex, anterior cingulate cortex, fusiform gyrus and hippocampus. All these FCs mediated the effect of sleep disturbance on pain and seven FCs mediated the effect of pain on sleep disturbance. The chronic pain PGS was positively associated with the FC between middle temporal gyrus and hippocampus, which further mediated the effect of chronic pain PGS on PSQI score. Mendelian randomization analysis implied a possible causal relationship from chronic pain to sleep disturbance was stronger than that of sleep disturbance to chronic pain. The results provided genetic and neural evidence for the association between pain and sleep disturbance, which may inform future treatment approaches for comorbid chronic pain states and sleep disturbance.

The Impact of Quarantine on Pain Sensation among the General Population in China during the COVID-19 Pandemic

“…We found that mental health symptoms were the largest risk factors for constant pain in the long-term quarantine population, indicating that pain could be a consequence of those mental health symptoms (effect b in Figure 1 ). These basic findings are consistent with research showing that psychological factors that are frequently comorbid with chronic pain also predispose patients to the development of chronic pain [ 4 , 6 ] and may in turn exacerbate and worsen pain symptoms. No social obligations and the lack of communication during quarantines did not result in more sleep; conversely, most people actually experienced worse quality sleep due to their damaged sleep schedules, stress and anxiety [ 39 ].…”

“…Although it is widely known that pain can cause mental health symptoms and sleep disturbances, we also need to realize that the interaction is bidirectional. Sleep disturbance could exacerbate pain via neurophysiological processes that modulate pain signaling at supraspinal and spinal levels [ 6 ].…”

“…Increasing evidence shows that psychological distress has important roles in central pain modulating mechanisms and exacerbates persistent chronic pain [ 5 ]. Genetic correlation and shared neural abnormalities of modulatory effects of the reciprocal relationships between pain sensation and mental disorder have been recognized [ 6 ]. Although the premise that quarantines may result in a high prevalence of mental issues is underscored by a growing body of epidemiological literature [ 7 , 8 , 9 , 10 ] and previous research found social isolation during the pandemic made chronic pain population suffering more [ 11 ].…”

Home-Based EEG Neurofeedback Intervention for the Management of Chronic Pain

“…Sleep disruption and chronic pain are comorbid disorders, with a survey of individuals suffering from fibromyalgia putting non-restorative sleep before pain in order of symptom severity ( 10 , 35 ). Therefore, both should be assessed when considering treatments/interventions and healthcare costs in people with chronic pain ( 36 ). Since there is evidence for the co-occurrence of sleep disturbance and chronic pain ( 10 ), treatment with neuromodulation may be a beneficial therapy for patients with both disorders, as suggested by our results.…”

Abnormal Visual Evoked Responses to Emotional Cues Correspond to Diagnosis and Disease Severity in Fibromyalgia

“…The role of impaired sleep in chronic pain is gaining more scientific focus in recent years. Accumulating evidence suggests that maladaptive sleep hampers both neural and molecular control mechanisms (e.g., Haack et al, 2020 ; Sun et al, 2020 ). Our results lend additional support for the relation between impaired neural connectivity and sleep disturbance, and in addition, highlight the role of affective attention in pain chronicity.…”