Longitudinal Pain Profiles and Their Clinical and Genetic Correlates in 624,996 U.S. Veterans
- 1Crescenz VA Medical Center
Abstract
ImportancePain varies in its intensity and course, yet much of our understanding of pain is based on cross-sectional assessments or longitudinal studies of selected clinical populations. Routinely collected electronic health record data may enable characterization of longitudinal pain patterns at scale.
ObjectiveTo identify longitudinal pain profiles among U.S. Veterans and characterize their clinical and polygenic correlates.
DesignCohort study using electronic health record and genomic data from the Million Veteran Program, with up to 16 years of pain assessments collected between 2000 to 2025.
SettingU.S. Department of Veterans Affairs health care system.
ParticipantsMillion Veteran Program participants assigned to African-like, Admixed American-like, East Asian-like, European-like, or South Asian-like genetically inferred ancestry groups who have at least three years of outpatient numeric rating scale pain records.
ExposuresOutpatient pain ratings and polygenic scores for psychiatric, sleep, and substance use traits.
Main Outcomes and MeasuresPain profiles were identified using Gaussian finite mixture modeling of pain intensity, directional change, and within-person variability. Profiles were characterized by pain, psychiatric and substance use diagnoses, opioid exposure, body mass index, and polygenic scores.
ResultsAmong 624,996 participants (Mean [SD] age at first pain rating=53.4 [13.5] years; 568,833 [91.0%] male), 51,731,567 outpatient pain ratings were analyzed. Three profiles were identified: stable no pain, stable mild pain, and mild-to-moderate increasing pain. Compared with the stable no pain profile, the increasing pain profile had higher odds of chronic pain (OR=21.14 [95% CI: 18.96-23.57]), opioid use disorder (OR=9.32 [95% CI: 8.31-10.45]), opioid exposure (OR=8.61 [95% CI: 8.41-8.83]), major depressive disorder (OR=3.77 [95% CI: 3.67-3.87]), and posttraumatic stress disorder (OR=3.72 [95% CI: 3.61-3.84]). Associations were attenuated but remained after adjustment for mean pain severity. Polygenic scores for depression, insomnia, attention-deficit/hyperactivity disorder, and tobacco use disorder were the most consistent predictors of increasing pain across the three largest genetically inferred ancestry groups.
Conclusions and RelevanceLongitudinal modeling of routinely collected pain scores identified pain profiles associated with clinical burden and polygenic liability. These profiles captured clinically meaningful information beyond mean pain severity alone, highlighting the value of longitudinal pain phenotyping in electronic health record data.
Key PointsO_ST_ABSQuestionC_ST_ABSCan pain scores collected in outpatient care identify clinically meaningful pain profiles among U.S. Veterans?
FindingsIn this cohort study of 624,996 Veterans with more than 51 million pain ratings across up to 16 years, three pain profiles were identified: stable no pain, stable mild pain, and mild-tomoderate increasing pain. Profiles differed in clinical burden even after accounting for mean pain severity and were associated with polygenic liability for psychiatric, sleep, and substance use traits.
MeaningRoutinely collected pain scores can be used to characterize heterogeneity in the course of pain and factors associated with more burdensome pain patterns.
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BibTeX
@misc{davis2026longitudinal,
title = {{Longitudinal Pain Profiles and Their Clinical and Genetic Correlates in 624,996 U.S. Veterans}},
author = {C. N. Davis and M. Shi and T. Gunawan and S. Toikumo and Million Veteran Program and J. Gray and H. Kranzler},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.10.26365209},
url = {https://www.medrxiv.org/content/10.64898/2026.10.10.26365209v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Longitudinal Pain Profiles and Their Clinical and Genetic Correlates in 624,996 U.S. Veterans
AU - C. N. Davis
AU - M. Shi
AU - T. Gunawan
AU - S. Toikumo
AU - Million Veteran Program
AU - J. Gray
AU - H. Kranzler
PY - 2026
DA - 2026/10/10
PB - medRxiv
DO - 10.64898/2026.10.10.26365209
UR - https://www.medrxiv.org/content/10.64898/2026.10.10.26365209v1
AB - ImportancePain varies in its intensity and course, yet much of our understanding of pain is based on cross-sectional assessments or longitudinal studies of selected clinical populations. Routinely collected electronic health record data may enable characterization of longitudinal pain patterns at scale. ObjectiveTo identify longitudinal pain profiles among U.S. Veterans and characterize their clinical and polygenic correlates. DesignCohort study using electronic health record and genomic data from the Million Veteran Program, with up to 16 years of pain assessments collected between 2000 to 2025. SettingU.S. Department of Veterans Affairs health care system. ParticipantsMillion Veteran Program participants assigned to African-like, Admixed American-like, East Asian-like, European-like, or South Asian-like genetically inferred ancestry groups who have at least three years of outpatient numeric rating scale pain records. ExposuresOutpatient pain ratings and polygenic scores for psychiatric, sleep, and substance use traits. Main Outcomes and MeasuresPain profiles were identified using Gaussian finite mixture modeling of pain intensity, directional change, and within-person variability. Profiles were characterized by pain, psychiatric and substance use diagnoses, opioid exposure, body mass index, and polygenic scores. ResultsAmong 624,996 participants (Mean [SD] age at first pain rating=53.4 [13.5] years; 568,833 [91.0%] male), 51,731,567 outpatient pain ratings were analyzed. Three profiles were identified: stable no pain, stable mild pain, and mild-to-moderate increasing pain. Compared with the stable no pain profile, the increasing pain profile had higher odds of chronic pain (OR=21.14 [95% CI: 18.96-23.57]), opioid use disorder (OR=9.32 [95% CI: 8.31-10.45]), opioid exposure (OR=8.61 [95% CI: 8.41-8.83]), major depressive disorder (OR=3.77 [95% CI: 3.67-3.87]), and posttraumatic stress disorder (OR=3.72 [95% CI: 3.61-3.84]). Associations were attenuated but remained after adjustment for mean pain severity. Polygenic scores for depression, insomnia, attention-deficit/hyperactivity disorder, and tobacco use disorder were the most consistent predictors of increasing pain across the three largest genetically inferred ancestry groups. Conclusions and RelevanceLongitudinal modeling of routinely collected pain scores identified pain profiles associated with clinical burden and polygenic liability. These profiles captured clinically meaningful information beyond mean pain severity alone, highlighting the value of longitudinal pain phenotyping in electronic health record data. Key PointsO_ST_ABSQuestionC_ST_ABSCan pain scores collected in outpatient care identify clinically meaningful pain profiles among U.S. Veterans? FindingsIn this cohort study of 624,996 Veterans with more than 51 million pain ratings across up to 16 years, three pain profiles were identified: stable no pain, stable mild pain, and mild-tomoderate increasing pain. Profiles differed in clinical burden even after accounting for mean pain severity and were associated with polygenic liability for psychiatric, sleep, and substance use traits. MeaningRoutinely collected pain scores can be used to characterize heterogeneity in the course of pain and factors associated with more burdensome pain patterns.
ER -