Chronic pain, its lifecourse origins in socioeconomic status, and the mediating role of chronic stress-related biomarkers

Each year, chronic pain (CP) significantly impacts various aspects of life and imposes a substantial burden on healthcare systems. Identifying risk factors for CP is crucial to alleviate the burden on individuals, inform preventive and interventional medical strategies, and reduce public health demands. While research has established socioeconomic inequalities in disease prevalence, studies examining the relationship between socioeconomic status (SES) and CP within the general population remain limited. In particular, limited research has addressed whether and how SES is associated with chronic pain. Given the close link between CP and dysregulated chronic stress, epidemiological survey data incorporating biomarkers offers new opportunities to explore this association. Investigating biomarkers of chronic stress dysregulation in relation to CP not only provides insight into how SES may contribute to CP but also adds valuable risk factor information to the broader field of pain epidemiology, aiding the development of precise pain management. Additionally, the lifecourse model, which explains the origins of chronic diseases by outlining how disease risk exposures at various life stages relate to future disease outcomes, holds promise for informing optimal timing for interventions. However, this model has not been thoroughly examined in the context of chronic pain. The first and second aims of this paper are to examine the associations between CP and biomarkers of chronic stress dysregulation. Typically, chronic stress dysregulation is reflected in dysregulation within the hypothalamic-pituitary-adrenal (HPA) axis and multisystem dysregulation, with the latter commonly measured through allostatic load (AL). These two investigations are essential, not only because they represent different mainstream measurements of chronic stress dysregulation but also because they provide detailed information on how localized and multisystem stress dysregulation may contribute to chronic pain, enriching prevention strategies. The third and fourth aims of this study investigate the association between lifecourse SES and CP, and separately examine the potential mediating roles of AL and salivary cortisol. To address these aims, we utilized different samples from the MIDUS study. Aim 1 examined the prospective relationship between AL, measured in the Biomarker Project of MIDUS 2 (2004-2006), and CP in MIDUS 3 (2013-2014). Aim 2 investigated the link between HPA axis dysregulation, as measured in the National Study of Daily Experiences (NSDE) of MIDUS 2, and CP in MIDUS 3. Aims 3 and 4 assessed the association between lifecourse SES and CP using three waves of MIDUS data spanning 20 years, with separate analyses examining the mediating roles of AL and salivary cortisol. For Aim 1, findings indicated that metabolic dysregulation phenotypes in AL were prospectively associated with high interference CP and with pain at three or more sites. In Aim 2, we found that among individuals without baseline chronic pain, those with blunted early and mid post-wake diurnal cortisol slopes (DCSs) had higher odds of developing pain in three or more regions approximately seven years later. In Aims 3 and 4, findings supported chain-of-risk models linking SES with the mid post-wake DCS and the cortisol dynamic range (CDR), suggesting that proximal adult socioeconomic disadvantage mediates the adverse effects of early-life disadvantage and directly impacts these cortisol indicators. Additionally, we identified a risk chain for metabolic dysregulation phenotypes in AL, with both childhood and recent SES directly linked to these phenotypes. Our results further substantiated a chain-of-risk model connecting lifecourse SES with CP interference, highlighting the mediating role of recent SES. For CP widespreadness, we found that the relationship between lifecourse SES and the number of pain sites may be contingent on the degree of multimorbidity. However, no mediating role of chronic stress biomarkers was observed.