Associations of pain phenotypes and pain relief medications with stroke and its subtypes: a prospective cohort study

Abstract This prospective study aimed to explore whether the associations between pain phenotypes, pain relief medications, and stroke risk differ by sex. We used data from 473,729 participants in the UK Biobank. Pain phenotypes were categorized as no pain, short-term pain, chronic localized pain (C...

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Main Authors: Yajie Zhu, Weidi Sun, Yuan Song, Dexter Canoy, Peige Song, Kazem Rahimi
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-04238-3
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author Yajie Zhu
Weidi Sun
Yuan Song
Dexter Canoy
Peige Song
Kazem Rahimi
author_facet Yajie Zhu
Weidi Sun
Yuan Song
Dexter Canoy
Peige Song
Kazem Rahimi
author_sort Yajie Zhu
collection DOAJ
description Abstract This prospective study aimed to explore whether the associations between pain phenotypes, pain relief medications, and stroke risk differ by sex. We used data from 473,729 participants in the UK Biobank. Pain phenotypes were categorized as no pain, short-term pain, chronic localized pain (CLP), and chronic widespread pain (CWP). Stroke events, including ischaemic stroke and haemorrhagic stroke, were identified through hospital and death records. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) for stroke, with interaction terms included to assess sex differences. We also evaluated the association between pain relief medications and stroke risk among the chronic pain subcohort. CWP was associated with higher stroke risks in both men (HR 1.36, 95% CI 1.11–1.65) and women (HR 1.31, 95% CI 1.08–1.60); however, women with CLP exhibited a significantly higher risk of stroke (HR 1.16, 95% CI 1.08–1.25) and ischaemic stroke (HR 1.18, 95% CI 1.09–1.28), while no significant associations between CLP and stroke and subtypes were observed in men (p for sex interactions < 0.001). Regarding pain relief, aspirin use was associated with an increased risk of stroke (HR 1.19, 95% CI 1.08–1.30), and opioid use was linked to a greater increase in the risk of subarachnoid haemorrhage (HR 1.92, 95% CI 1.25–2.95). Chronic pain phenotypes, particularly in women and individuals with multiple CLP sites and CWP, were significantly associated with increased risks of stroke. Use of aspirin and opioids was also associated with higher stroke risks.
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spelling doaj-art-ddd359f4fd2f4d82bdf5ff20bc9120922025-08-20T03:45:27ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-04238-3Associations of pain phenotypes and pain relief medications with stroke and its subtypes: a prospective cohort studyYajie Zhu0Weidi Sun1Yuan Song2Dexter Canoy3Peige Song4Kazem Rahimi5School of Information Science and Technology, Hangzhou Normal UniversityCenter for Clinical Big Data and Statistics of the Second Affiliated Hospital Zhejiang University School of Medicine, School of Public Health, Zhejiang University School of MedicineSchool of Nursing and Health, Zhengzhou UniversityPopulation Health Sciences Institute, Newcastle UniversityCenter for Clinical Big Data and Statistics of the Second Affiliated Hospital Zhejiang University School of Medicine, School of Public Health, Zhejiang University School of MedicineNuffield Department of Women’s and Reproductive Health, Medical Science Division, University of OxfordAbstract This prospective study aimed to explore whether the associations between pain phenotypes, pain relief medications, and stroke risk differ by sex. We used data from 473,729 participants in the UK Biobank. Pain phenotypes were categorized as no pain, short-term pain, chronic localized pain (CLP), and chronic widespread pain (CWP). Stroke events, including ischaemic stroke and haemorrhagic stroke, were identified through hospital and death records. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) for stroke, with interaction terms included to assess sex differences. We also evaluated the association between pain relief medications and stroke risk among the chronic pain subcohort. CWP was associated with higher stroke risks in both men (HR 1.36, 95% CI 1.11–1.65) and women (HR 1.31, 95% CI 1.08–1.60); however, women with CLP exhibited a significantly higher risk of stroke (HR 1.16, 95% CI 1.08–1.25) and ischaemic stroke (HR 1.18, 95% CI 1.09–1.28), while no significant associations between CLP and stroke and subtypes were observed in men (p for sex interactions < 0.001). Regarding pain relief, aspirin use was associated with an increased risk of stroke (HR 1.19, 95% CI 1.08–1.30), and opioid use was linked to a greater increase in the risk of subarachnoid haemorrhage (HR 1.92, 95% CI 1.25–2.95). Chronic pain phenotypes, particularly in women and individuals with multiple CLP sites and CWP, were significantly associated with increased risks of stroke. Use of aspirin and opioids was also associated with higher stroke risks.https://doi.org/10.1038/s41598-025-04238-3Body painStrokePain reliefSex difference
spellingShingle Yajie Zhu
Weidi Sun
Yuan Song
Dexter Canoy
Peige Song
Kazem Rahimi
Associations of pain phenotypes and pain relief medications with stroke and its subtypes: a prospective cohort study
Scientific Reports
Body pain
Stroke
Pain relief
Sex difference
title Associations of pain phenotypes and pain relief medications with stroke and its subtypes: a prospective cohort study
title_full Associations of pain phenotypes and pain relief medications with stroke and its subtypes: a prospective cohort study
title_fullStr Associations of pain phenotypes and pain relief medications with stroke and its subtypes: a prospective cohort study
title_full_unstemmed Associations of pain phenotypes and pain relief medications with stroke and its subtypes: a prospective cohort study
title_short Associations of pain phenotypes and pain relief medications with stroke and its subtypes: a prospective cohort study
title_sort associations of pain phenotypes and pain relief medications with stroke and its subtypes a prospective cohort study
topic Body pain
Stroke
Pain relief
Sex difference
url https://doi.org/10.1038/s41598-025-04238-3
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