Mental Health

Co-occurring chronic pain and opioid use disorder diagnoses in the All of Us Research Program: associations with social determinants of health, mental health conditions, and polygenic liability.

Johnson E, Luo Z, et al. • EBioMedicine • 2026

PubMed 42114418 DOI 10.1016/j.ebiom.2026.106273

TL;DR

Co-occurring chronic pain and OUD diagnoses were associated with fewer years of education, lower income, greater likelihood of other psychiatric diagnoses, and higher polygenic scores for both chronic pain and OUD, suggesting that socioeconomic hardship and co-occurring mental health conditions are correlates of risk for co-occurring chronic pain and OUD.

Key Findings

Results

Among participants with co-occurring chronic pain and OUD diagnoses, chronic pain preceded OUD in the majority of cases.

Chronic pain diagnosis preceded OUD in 57% of co-occurring cases
43% of cases received an OUD diagnosis at the same time as or before the chronic pain diagnosis
Data source was the All of Us Research Program (AoU) Release 8
Analysis was cross-sectional in design

Results

Participants whose chronic pain diagnosis came first differed clinically from those with simultaneous or prior OUD diagnosis.

Those with chronic pain diagnosed first were less likely to have a PTSD diagnosis
They were less likely to report using prescription opioids for non-prescribed purposes
However, they had a greater number of opioid prescriptions recorded in their records

Results

Co-occurring chronic pain and OUD diagnoses were associated with socioeconomic disadvantage compared to chronic pain alone.

Co-occurring diagnoses were associated with fewer years of education relative to chronic pain alone
Co-occurring diagnoses were associated with lower income relative to chronic pain alone
Co-occurring diagnoses were associated with greater likelihood of other psychiatric diagnoses relative to chronic pain alone
Co-occurring diagnoses were associated with higher polygenic scores for both chronic pain and OUD relative to chronic pain alone

Results

Co-occurring chronic pain and OUD diagnoses were distinguished from OUD-only diagnoses by specific mental health and polygenic liability profiles.

Greater likelihood of an anxiety diagnosis was associated with co-occurring chronic pain and OUD compared to OUD alone
Higher polygenic liability for chronic pain was associated with co-occurring diagnoses compared to OUD alone
Lower polygenic liability for OUD was associated with co-occurring diagnoses compared to OUD alone

Results

Polygenic scores for both chronic pain and OUD were independently elevated in participants with co-occurring diagnoses.

Higher polygenic scores for chronic pain were associated with co-occurring chronic pain and OUD diagnoses versus chronic pain alone
Higher polygenic scores for OUD were associated with co-occurring chronic pain and OUD diagnoses versus chronic pain alone
In contrast, those with co-occurring diagnoses had lower OUD polygenic liability than those with OUD alone, suggesting a distinct genetic profile
Analyses used AoU Release 8 genomic and clinical data

Background

Most current OUD cases in the US stem from non-prescribed opioids, occurring in a context of declining outpatient opioid prescribing.

Outpatient prescribing of opioids in the US has declined over the past decade
Most OUD cases now stem from non-prescribed opioids such as fentanyl
Despite this shift, the risk of developing opioid dependence from prescribed opioids remains a concern
Chronic pain is described as a public health burden and opioids remain among the strongest analgesics available

What This Means

This research used a large, diverse U.S. dataset called the All of Us Research Program to examine people who had been diagnosed with both chronic pain and opioid use disorder (OUD). The study found that in most cases (57%), chronic pain was diagnosed before OUD, while in 43% of cases the OUD diagnosis came at the same time or even earlier than the chronic pain diagnosis. People whose chronic pain came first tended to have more opioid prescriptions on record but were less likely to have PTSD or to report misusing prescription opioids, compared to those who received an OUD diagnosis first or simultaneously. The study also found that having both chronic pain and OUD together — compared to having only chronic pain — was linked to lower income, fewer years of education, a higher chance of having other psychiatric conditions, and higher genetic risk scores for both chronic pain and OUD. When comparing people with both diagnoses to those with OUD alone, the co-occurring group was more likely to have an anxiety diagnosis and showed a different genetic risk profile: higher genetic liability for chronic pain but, interestingly, lower genetic liability for OUD. This research suggests that social and economic hardship, mental health conditions like anxiety and PTSD, and genetic predispositions all play a role in who develops both chronic pain and OUD at the same time. The authors emphasize that future prevention and treatment efforts should prioritize addressing socioeconomic challenges and co-occurring mental health conditions, rather than focusing solely on opioid prescribing patterns.

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Citation

Johnson E, Luo Z, Romero Villela P, Kadaba S, Sarabudla N, Balbona J, et al.. (2026). Co-occurring chronic pain and opioid use disorder diagnoses in the All of Us Research Program: associations with social determinants of health, mental health conditions, and polygenic liability.. EBioMedicine. https://doi.org/10.1016/j.ebiom.2026.106273

Key Findings

What This Means

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