Chronic pain and cardiovascular risk: is there a connection?
Chronic pain affects millions of people worldwide and remains one of the leading causes of disability. Beyond its direct impact on quality of life, chronic pain is frequently accompanied by other serious conditions, including anxiety, depression, fatigue and cardiovascular disease. However, the biological mechanisms driving this clustering of diseases remain poorly understood.
Exploring pain at population scale
The EU-funded PainFACT(opens in new window) project set out to address this gap and uncover the hidden links between pain and multimorbidity. The consortium analysed health data from more than five million individuals across Norway. It also included large international population studies, such as the UK Biobank(opens in new window) and the Danish Blood Donor Study(opens in new window). In addition, a unique and genetically diverse mouse cohort was used to experimentally investigate molecular associations between pain and comorbidities. Researchers integrated patient registries, genetics, blood protein measurements and imaging data. They then investigated how chronic pain co-occurs with other diseases and which biological pathways may underlie these relationships. “Chronic pain is often viewed as an isolated condition, but our findings show that it is deeply interconnected with broader systemic health. Understanding these links is essential if we want to improve both diagnosis and treatment,” explains project coordinator Christopher Sivert Nielsen.
Links to cardiovascular disease
Among the project’s most important findings was the strong association between chronic pain and future cardiovascular disease. While previous research has largely focused on psychiatric comorbidities, PainFACT identified elevated cardiovascular risk as a major feature of chronic pain disorders. The association was especially pronounced in conditions such as fibromyalgia(opens in new window). Individuals with increased pain sensitivity also showed a higher risk of cardiovascular disease, even after accounting for traditional risk factors such as smoking, cholesterol levels and hypertension. These findings may be particularly significant for women, who are disproportionately affected by chronic pain disorders and often experience different symptoms during cardiovascular events. “The relationship between pain sensitivity and cardiovascular disease may provide an important clue to understanding female-specific cardiovascular risk and influence how this risk is identified and managed in clinical practice,” emphasises Nielsen.
Shared mechanisms
The PainFACT project also carried out the first large-scale genome-wide association study of pain sensitivity using the cold-pressor test, an experimental method measuring tolerance to cold-induced pain. Researchers analysed data from approximately 30 000 participants and identified five genes associated with pain tolerance. One of the most notable was the TRPM8(opens in new window) gene, which is involved not only in pain perception but also in blood pressure regulation. Further analyses revealed strong genetic overlap between pain sensitivity, chronic pain conditions such as migraine and coronary artery disease. This overlap suggests that chronic pain and cardiovascular disease may share common biological pathways rather than representing entirely separate conditions. The cold-pressor test itself emerged as an important methodological advance. According to Nielsen, “Establishing the cold-pressor test as a tool for molecular discovery is one of the project’s major achievements. It will help us understand how pain mechanisms interact with cardiovascular biology.” By uncovering previously unrecognised links between chronic pain and systemic disease, PainFACT aims to redefine the concept of pain as a complex, multisystem condition. Looking ahead, researchers plan to expand genetic studies of pain sensitivity and focus further on cardiovascular comorbidity.
