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

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.