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, Emma C; Luo, Zhen; Romero Villela, Pamela N; Kadaba, Sukruth; Sarabudla, Nithya; Balbona, Jared V; Goodin, Burel R; Haroutounian, Simon et al. · EBioMedicine · 2026

cross_sectional · Level IV

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Abstract

Chronic pain is a public health burden, and opioids remain among the strongest analgesics available. While outpatient prescribing of opioids in the US has declined in the past decade, and most opioid use disorder (OUD) cases now stem from non-prescribed opioids (e.g., fentanyl), the risk of developing opioid dependence remains a concern. To assess the prevalence of co-occurring chronic pain and OUD diagnoses in the All of Us Research Program (AoU) and the role of genetic liability and social determinants of health, we performed cross-sectional analyses on AoU Release 8 data. Of participants with co-occurring chronic pain and OUD diagnoses, the chronic pain diagnosis preceded OUD in 57% of cases, while 43% of cases received an OUD diagnosis at the same time or before the chronic pain diagnosis. Participants whose chronic pain diagnosis came first were less likely to have a PTSD diagnosis and were less likely to report using prescription opioids for non-prescribed purposes, but had a greater number of opioid prescriptions recorded. Relative to a diagnosis of chronic pain alone, 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 chronic pain and OUD. Greater likelihood of an anxiety diagnosis, higher polygenic liability for chronic pain, and lower polygenic liability for OUD were associated with co-occurring diagnoses of chronic pain and OUD compared to only a diagnosis of OUD. Our results suggest that socioeconomic hardship and co-occurring mental health conditions are correlates of risk for co-occurring chronic pain and OUD; these areas should be prioritised in future research to improve prevention and treatment outcomes. R03DA059747 (ECJ); Department of Anesthesiology Training Grant R90NR021799 (PNRV, BG, ECJ); K01AA030083 (ASH).