The study of the relationship between socioeconomic dislocation and individual anomic behavior and experiences can be traced back to the inception of sociology (1). Over the past half-century, the American socioeconomic structure has undergone a gradual decline concomitant with the process of deindustrialization and continuous trade disadvantages, which has precipitated a surge in anomic phenomena known as “deaths of despair” (2), which encompass suicides, drug overdoses, and alcoholism deaths among middle-age individuals (3). Coincidentally, the prevalence of chronic pain (CP) among Americans has also increased during the same period (4–7). The conjugate trend underscores the necessity of examining the relationship between socioeconomic disadvantages (SEDs) and CP because CP may not only serve as the intermediary mechanism connecting socioeconomic collapse with the deaths of despair (8, 9) but also play a pivotal role in engendering a more extensive public burden (10). The International Association for the Study of Pain (IASP) defines CP as pain that persists or recurs for more than 3 months (11). A meta-analysis indicates that CP affects approximately 43.5% of the general population in the United Kingdom (12). In the United States, approximately 20.5% of adults suffer from CP each year, which causes substantial burdens on the national health system as well as a considerable productivity loss of over $296 billion (10).

CP is suggested to be a crucial factor in suicides related to deaths of despair (8). Both CP and deaths of despair seem to share an antecedent cause—protracted socioeconomic turmoil. SED reflects an individual's or a group's lower position in the social hierarchy, characterized by their limited economic and social resources, and it encompasses facing economic hardships, social inequality, and reduced access to resources and opportunities compared with more advantaged social groups (13, 14). For decades, SED has been identified as the fundamental cause of chronic disease disparities between different social groups (13). The fundamental cause theory posits that the unequal distribution of flexible resources among individuals is the main driving force for the varying vulnerability of distinct social groups to diseases (13). The accumulation of risk model further links life course SED to health disparities (15). Individuals who consistently face SED are at a heightened risk of exposure to detrimental stressors, or SED can be considered the persistent stressor itself (16), increasing the probability of experiencing CP. Furthermore, the social mobility framework integrates the temporal variations in the level of SED experienced during different stages of life into the accumulation of risk model. The social mobility model elucidates the progression of individuals as they move up or down the social class ladder throughout their entire life span (17, 18). Recent studies have corroborated the trajectory of SED on health outcomes: descending SED is positive for one's wellbeing (19, 20), and the detrimental effect of early-life adversity can be alleviated or even reversed by upward social mobility (21, 22).

A previous topical review has revealed substantial evidence of a statistically significant association between SED and an increased prevalence of CP, elevated levels of pain interference, and a greater extent of CP widespreadness (23). Few cohort studies prospectively examined the differential impacts of life course SEDs on CP widespreadness (24–26) and the recent cohort studies have several limitations. First, only a few population-based prospective studies have investigated the association between SED and pain interference. Similar to the number of pain sites, pain interference is closely linked to functional limitations in patients in pain (27), and such limitations provoke physical, psychological, and societal issues in an individual’s life (28). Thus, it is necessary to incorporate pain interference and the number of pain sites in the examination. Second, chronic illnesses have not been considered a substantial confounder influencing SED (29) and CP (30). In addition, although population-based research on social mobility and low back pain (pain lasting 7 days or more in the past 12 months) exists, the study did not utilize the definition of CP in terms of its duration (31). Therefore, the trajectories of SED link to CP remain unknown. Finally, previous studies have explored the mediation mechanisms of psychological distress (25) and obesity (26), but how SEDs are prospectively linked with CP through sociobiological mechanisms remains unknown.

Allostatic load (AL) is defined as the physiological wear and tear arising from repeated adaptations to chronic stressors (32). It begins with the prolonged activation of the hypothalamus–pituitary–adrenal (HPA) axis and sympathetic nervous system and culminates with elevated levels of glucocorticoids and catecholamines. Over time, the excessive accumulation of these substances can have downstream repercussions and contribute to subclinical or clinical conditions affecting the cardiovascular, metabolic, and immune systems. AL may provide a biosocial framework bridging SED and CP. First, individuals subjected to prolonged SEDs or deteriorating trajectories of such adversities are prone to trigger chronic stress responses and dysregulation across multiple physiological systems (33). In accordance with the theory, several years of empirical evidence consistently show that people who report more SED have higher AL levels (34, 35). Second, the pathology of CP is associated with the physiological dysregulation of systems related to AL (36–38). Specifically, the excessive activation of the HPA axis and sympathetic nervous system, accompanied by subsequent sustained pro-inflammatory states, is related to central sensitization and alterations in pain signaling pathways, resulting in the occurrence or maintenance of nociception (37, 39). Despite the compelling theory linking AL and CP, research investigating the correlation between these two factors, especially in terms of prospective population-based studies, remains scarce. Previous studies have indicated that CP was associated with the dysregulation of the biological stress response to chronic stress (38, 40). Cross-sectional studies based on population samples have discovered that elevated AL was associated with higher levels of CP severity and an increased risk of its occurrence (41, 42). However, previous studies did not incorporate HPA axis biomarkers in constructing AL (42), and the definition of CP used in other studies lacked time specificity (41). Moreover, early CP (30) and medication use (43) were not adjusted for.

Childhood has been recognized as a critical period in both the risk accumulation and social mobility models, and childhood SED could act as a moderator in the association between AL and CP. The critical period emphasizes that during childhood, which is considered a window of biological development, the experience of adversity can have long-lasting and irreversible effects on physiological functions (44). Numerous studies indicate that exposure to chronic stress during the critical period can alter the normal development of the stress response system (45) and disrupt the pain processing pathway (46), thereby exacerbating poor stress responses and amplifying the effects of stress on pain perception in adulthood. Although previous research on the critical period has emphasized the biological consequences of childhood disadvantage and emerging literature has revealed the long-term harmful effects of SED on AL and CP (23, 47), whether the biological long arm of childhood SED magnifies the impacts of chronic stress response on CP in adulthood remains unclear.

Overall, the present research aimed to examine three goals. The first goal was to test whether cumulative SED and SED trajectory would have a prospective association with future CP outcomes. Second, in preparation for mediation analysis, the present study aimed to examine whether SED and SED trajectory would be prospectively related to AL and examine whether AL would be associated with future CP outcomes. Also, the moderation effect of childhood SED on the association between AL and CP was tested. The third goal was to test whether AL would mediate the association between SED and CP, Furthermore, the study aimed to examine whether mediation analyses would be moderated by childhood SED.

This study utilized the MIDUS national survey to examine the prospective associations between SED and CP. The results indicated a significant association between proximal SED and high-interference CP, but not between the whole life course accumulation of SED and future CP. Also, individuals with a worsening SED trajectory had a higher risk of high-interference pain and 3+ chronic pain sites. There is a positive correlation between cumulative SED and AL, and an improving trajectory of SED has a protective effect on AL. The association between AL and CP was initially not found significant, but after adding the interaction term of childhood SED and AL, the association became significant. Specifically, childhood SED may reduce the impact of AL on CP. Finally, no mediating effect of AL was found.

Previous studies have found that economic difficulties at age 43 and cumulative economic difficulties at ages 43 and 60–64 were associated with chronic widespread pain at age 68 (24). Similarly, another study found that occupational status at age 42 was associated with chronic widespread pain at age 45 (26). However, we did not find similar associations between cumulative SED and CP widespreadness. Compared with the studies mentioned, this study has several advantages that may contribute to the difference. We attempted to capture the multidimensional aspects of SED by integrating both subjective and objective SEDs rather than relying on a single socioeconomic indicator (72, 73). In addition, we considered various confounders to eliminate spurious associations. For example, disease diagnoses can reduce employment chances and working hours (74) and harm future health outcomes and social status (29). Therefore, chronic disease exacerbates SED and triggers CP conditions (30), leading to a false association. Furthermore, a different measure of CP widespreadness may contribute to the null association. Previous studies relied on the 1990 American College of Rheumatology standard (24, 26), while our measure utilized the 2016 revision criteria (75), which involved the use of the widespread pain index. However, both pain measurement methods utilized in the previous literature and in the MIDUS study were merely approximations of clinical pain assessment.

This study found that only MIDUS 2 SED was prospectively associated with high-interference CP at MIDUS 3; therefore, the results did not support the lifetime accumulation of risk model. This finding is consistent with previous research on life course SED and health outcome. A long-term cohort study of individuals who graduated from high school in Wisconsin in 1957 showed that only proximal socioeconomic status was associated with later mortality (22). The results of the present study corroborate previous research indicating that subsequent socioeconomic resources completely mediate the impacts of early SED on CP. Furthermore, in line with prior research, our results indicated that increased SEDs are related to elevated levels of CP interference (76–78). The recent accumulation of SED has exposed individuals to a high risk environment for CP and limited access to immediate resources for CP management. This could be one explanation for this association. Moreover, pain interference encompasses not only the intensity of pain but also the perceptions and beliefs of an individual about their pain (79). Individuals with recent socioeconomic advantages may hold more positive attitudes toward their health and possess greater self-efficacy in managing it, thereby contributing to a more favorable assessment of pain interference (80).

To our knowledge, our study is the first to use rigorously defined measures of CP to ascertain a prospective association of SED trajectories with CP within a community-dwelling sample. We used LCTM to standardize the trajectory phenotype of SED from heterogeneous data, providing a robust and reproducible tool for measuring SED trajectories (57), which supplements the limited literature on social mobility and CP. Our results support the social mobility model of CP development. The results indicated that individuals experiencing continuous worsening of SED over the years were more likely to have more CP sites and high-interference pain. A study found that a low socioeconomic trajectory was associated with high pain interference (81). However, SED trajectories were constructed using binary measures for three periods, which may result in an overclassified group number and groups with very few respondents. Another study refined the classification approach of unsecured debt-to-income ratio trajectories through a group-based trajectory model. They revealed that individuals who experienced trajectories of more unsecured debt were more susceptible to reporting joint problems and pain interference compared with those with minimal or no debt (82). However, both studies assessed pain experienced over the past 4 weeks rather than pain persisting for more than 3 months, resulting in the measure including trivial and recent pain. Our rigorous use of measures defined based on CP criteria eliminates much measurement error that previous studies with vague measures of CP duration have, thereby significantly enhancing our comprehension of the link between SED trajectories and CP.

Also, compared with those who remained in a prolonged state of advantage, no significant association was found between an improving SED trajectory and CP, even among individuals who experienced a highly disadvantaged childhood. One study found that an upward income trajectory can mitigate the adverse impacts of early-life disadvantages on physical health (19). Therefore, positive social mobility may enhance an individual’s access to flexible resources, which in turn enables them to adopt more proactive pain-coping strategies and cultivate healthy social relationships. As a result, this has the potential to alleviate the detrimental effects of early SED on the development of CP in the future. It could explain the null association between the trajectory characterized by high SED early in life transitioning to low SED later in life and CP.

This study may also be the first to explore the prospective association between AL and CP using population-based samples. Our results indicated that the relationship was initially statistically insignificant, but the association became significant when the interaction term of AL and childhood SED was added. On the one hand, as a critical period, childhood disadvantage can alter long-term pain processing, including sensitizing nociceptive pathways and lowering adulthood pain thresholds (46). In addition, early-life chronic stress can chronically change the function of the HPA axis, resulting in a pronociceptive effect (45, 46). As indicated by our results, childhood SED increases the risk of having AL, and AL was prospectively associated with having no less than three CP sites in the presence of the synergistic effect of SED and AL. On the other hand, we have discovered a counterintuitive phenomenon that childhood SED has a protective effect on at least three CP sites. One explanation is the development of resilience during childhood. Being resilient refers to the ability to effectively deal with the aftermath of risks, overcome the effects of traumatic events, and avoid harmful paths that frequently accompany risky circumstances (83). Childhood is a plastic period for developing resilience, and children raised in socioeconomically deprived environments may acquire coping skills and tactics that empower them to handle stress and adversity, potentially mitigating the harmful impact of disadvantage on their health (84–86), including CP (87, 88).

Only one community-dwelling study examined the mediating effect of AL on the cross-sectional association between SED and CP (42), and the findings indicate that the mediating effect was not significant. Similarly, when employing an introduced counterfactual framework in the mediation analysis, we did not find a significant prospective mediating effect of AL while controlling for additional confounders. The non-significant mediating effect may be related to the following reasons or limitations. First, different CP syndromes exhibit distinct underlying pathologies. The recent classification of CP (ICD-11) distinguishes between two broad categories (11), namely, chronic primary pain (also referred to as nociplastic pain) and chronic secondary pain (also categorized as nociceptive pain and neuropathic pain). Chronic primary pain is characterized by persistent or recurring pain in one or more anatomical regions lasting longer than 3 months (11). It is accompanied by significant emotional distress or functional interference, impacting daily activities and social engagement. This type of pain is not attributable to another specific CP condition (11) and is often associated with maladaptive stress responses (89). However, the CP measure in our study may have captured chronic secondary pain, which arises directly from underlying conditions such as cancer, stroke, diabetic neuropathy, and other related ailments (11). This is because our findings demonstrated a significant association between the chronic disease index and CP conditions (results not presented), indicating that diseases predominantly induced the pain. Future research can improve the analysis of AL as a mediator by using specific types of CP, such as migraine (36). Nevertheless, it is important to acknowledge that even for identical CP types, pain pathological traits may vary depending on the course, such as HPA dysfunction manifestation being associated with degrees of muscle pain distribution (38).

Second, this operationalization has limitations even if we measured AL using rigorously collected biomarkers that included the primary mediator system and calculated the AL index using classical additive methods. This additive method assumes that stressors have an equal impact on each high-risk biomarker or that each biomarker is equally crucial for outcomes. In addition, how the biomarkers of each score are combined is not clear. Alternative methods include latent class analysis and latent profile analysis. They can detect the dysregulation pattern of physiological systems driving AL (90). However, both latent class analysis and latent profile analysis come with their own set of challenges. One challenge is the exploratory nature of these analyses, which means that subjectivity often involves selecting the final model and qualitatively naming the clusters. We encourage future research to use advanced algorithms to narrow the gap between operationalization and theoretical implications.

There are also limitations to our sample. While the demographic and health traits of the biomarker project sample closely resemble those of the national survey sample (91), our longitudinal data containing biomarker project samples lack representation of ethnic minorities. Daily stress, such as discrimination, can amplify the CP inequality experienced by African Americans in the incidence of CP and medical practices (92). Therefore, future research should supplement the study of minority ethnic samples. In addition, childhood indicators were retrospectively collected. Some studies have validated the concordance of childhood socioeconomic indicators in the MIDUS study using sibling samples and a sample of twins, and the results indicated that the concordance of recall measures was generally high (93). However, prospective childhood indicators are still recommended in future research due to retrospective biases.

This study revealed the prospective associations between recent SED and future CP reports despite limitations. Also, the present study supports the social mobility model of CP. Furthermore, childhood, as a critical developmental period, provides advantages in developing resilience to adversity through the experience of SED. However, this resilience comes at a cost, as it interacts with AL and increases the risk of multisite pain in adulthood. Overall, increasing opportunities for positive social mobility and reducing childhood and recent SED may be key to mitigating inequalities in CP. Future research might investigate SED and CP connections by refining CP and AL measurements or scrutinizing other sociobiological processes.