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Abstract Chronic overlapping pain conditions (COPCs) affect a wide population and incur a substantial disease burden including comorbid mental disorders. Although these comorbidities have been extensively documented, the longitudinal trajectories of their onset, particularly for those with three or more conditions, have been rarely studied. We conducted retrospective cohort studies to identify statistically significant COPCs and mental health trajectories in the All of Us Research Program (AoU v8, 338,170 persons) and the Mayo Data Warehouse (3,957,444 individuals). For each trajectory, cases were matched with controls by demographic factors. Logistic regression was then applied to assess the increased likelihood of the final condition given the prior conditions in that sequence. The significant trajectories were visualized as a “pain forest.” More than 88% of trajectories identified from AoU (Male: 78, Female: 361) were reproducible in the Mayo Data Warehouse data (Male: 361, Female: 1286), with female trajectories encompassing more than 96% of the male trajectories. The findings indicate that chronic low back pain generally occurs earlier than other conditions, while fibromyalgia tends to follow other COPCs. Endometriosis seems to be associated with an increased prevalence of COPCs in women. In addition, longer trajectories are associated with a greater risk of developing additional COPC or mental condition. The results offer new insights into the progression of COPCs and associated mental conditions, which may inform healthcare providers and patients in managing and preventing exacerbation of these conditions.
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This content will become publicly available on June 17, 2026
Sociodemographically differential patterns of chronic pain progression revealed by analyzing the all of us research program data
The differential progression of ten chronic overlapping pain conditions (COPC) and four comorbid mental disorders across demographic groups have rarely been reported in the literature. To fill in this gap, we conducted retrospective cohort analyses using All of Us Research Program data from 1970 to 2023. Separate cohorts were created to assess the differential patterns across sex, race, and ethnicity. Logistic regression models, controlling for demographic variables and household income level, were employed to identify significant sociodemographic factors associated with the differential progression from one COPC or mental condition to another. Among the 139 frequent disease pairs, we identified group-specific patterns in 15 progression pathways. Black or African Americans with a COPC condition had a significantly increased association in progression to other COPCs (CLBP- > IBS, CLBP- > MHA, or IBS- > MHA, OR≥1.25, adj.p ≤ 4.0x10-3) or mental disorders (CLBP- > anxiety, CLBP- > depression, MHA- > anxiety, MHA- > depression, OR≥1.25, adj.p ≤ 1.9x10-2) after developing a COPC. Females had an increased likelihood of chronic low back pain after anxiety and depression (OR≥1.12, adj.p ≤ 1.5x10-2). Additionally, the lowest income bracket was associated with an increased risk of developing another COPC from a COPC (CLBP- > MHA, IBS- > MHA, MHA- > CLBP, or MHA- > IBS, OR≥1.44, adj.p ≤ 2.6x10-2) or from a mental disorder (depression- > MHA, depression- > CLBP, anxiety- > CLBP, or anxiety- > IBS, OR≥1.50, adj.p ≤ 2.0x10-2), as well as developing a mental disorder after a COPC (CLBP- > depression, CBLP- > anxiety, MHA- > anxiety, OR≥1.37,adj.p ≤ 1.6x10−2). To our knowledge, this is the first study that unveils the sociodemographic influence on COPC progression. These findings suggest the importance of considering sociodemographic factors to achieve optimal prognostication and preemptive management of COPCs.
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- PAR ID:
- 10616914
- Editor(s):
- Rentería, Miguel E
- Publisher / Repository:
- the Public Library of Science (PLOS)
- Date Published:
- Journal Name:
- PLOS Digital Health
- Volume:
- 4
- Issue:
- 6
- ISSN:
- 2767-3170
- Page Range / eLocation ID:
- e0000687
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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