Pain
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Chronic pain conditions frequently co-occur, suggesting common risks and paths to prevention and treatment. Previous studies have reported genetic correlations among specific groups of pain conditions and reported genetic risk for within-individual multisite pain counts (≤7). Here, we identified genetic risk for multiple distinct pain disorders across individuals using 24 chronic pain conditions and genomic structural equation modeling (Genomic SEM). ⋯ Annotation identified pathways associated with organogenesis, metabolism, transcription, and DNA repair, with overrepresentation of strongly associated genes exclusively in brain tissues. Cross-reference with previous GWASs showed genetic overlap with cognition, mood, and brain structure. These results identify common genetic risks and suggest neurobiological and psychosocial mechanisms that should be targeted to prevent and treat cross-condition chronic pain.
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Exposure to severely stressful events during childhood is associated with poor health outcomes in later life, including chronic pain and substance use disorder. However, the mediators and mechanisms are unclear. We investigated the impact of a well-characterized mouse model of early-life adversity, fragmented maternal care (FC) between postnatal day 2 and 9, on nociception, inflammatory hypersensitivity, and responses to morphine. ⋯ However, after an initial recovery of mechanical hypersensitivity, there was a reappearance in mice exposed to FC by day 15, which was not seen in control mice. Changes in nociception, morphine responses, and hypersensitivity associated with FC were apparent in males and females but were absent from mice lacking δ receptors or β-arrestin2. These findings suggest that exposure to early-life adversity in mice enhances δ receptor expression leading to decreased basal sensitivity to noxious stimuli coupled with accelerated morphine tolerance and enhanced vulnerability to persistent inflammatory hypersensitivity.
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Despite growing recognition of the importance of social, economic, and political contexts for population health and health inequalities, research on pain disparities relies heavily on individual-level data, while neglecting overarching macrolevel factors such as state-level policies and characteristics. Focusing on moderate or severe arthritis-attributable joint pain-a common form of pain that considerably harms individuals' quality of life-we (1) compared joint pain prevalence across US states; (2) estimated educational disparities in joint pain across states; and (3) assessed whether state sociopolitical contexts help explain these 2 forms of cross-state variation. We linked individual-level data on 407,938 adults (ages 25-80 years) from the 2017 Behavioral Risk Factor Surveillance System with state-level data on 6 measures (eg, the Supplemental Nutrition Assistance Program [SNAP], Earned Income Tax Credit, Gini index, and social cohesion index). ⋯ Educational gradients in joint pain exist in all states but vary substantially in magnitude, primarily due to variation in pain prevalence among the least educated. At all education levels, residents of states with greater educational disparities in pain are at a substantially higher risk of pain than peers in states with lower educational disparities. More generous SNAP programs (odds ratio [OR] = 0.925; 95% confidence interval [CI]: 0.963-0.957) and higher social cohesion (OR = 0.819; 95% CI: 0.748-0.896) predict lower overall pain prevalence, and state-level Gini predicts higher pain disparities by education.