Chronic pain and blood chemistry linked to brain disorders
A prospective cohort study of 174,630 UK Biobank participants linked a pain-related blood pattern to depression, anxiety and stroke over a median 15.6 years.
Our read
Mechanisms- Studied:
- Cohort study of 174,630 UK Biobank participants, median 15.62 years (Multicenter)
- What changed:
- Depression risk was higher with a higher pain-related blood chemistry score (hazard ratio 1.09), after accounting for pain sites
- The catch:
- Developing neurological or psychiatric conditions could have influenced the baseline blood metabolic signature
- In the record:
- The 11th paper on metabolic signatures with results in people; 16 on record in all.
Editor of record: Boris Djordjevic · AgingResearch.News
UK Biobank participants—174,630 people without brain disorders at entry—were followed in a prospective cohort study. Their average age was 56.56 years, and 54.19% were male. Questionnaires assessed pain lasting more than three months at seven body sites. Researchers combined 88 blood metabolites, small molecules produced or used by the body, into a pain-related score.
Over a median 15.6 years, more pain sites and higher scores were linked to higher risks of depression, anxiety and ischemic stroke. In this type of stroke, blood flow to part of the brain is blocked. Statistical models suggested that inflammation-related blood counts partly accounted for the score’s links to depression (4.33%) and stroke (9.52%). A Mendelian randomization analysis, which uses genetic differences to examine disease links, also associated several metabolites with these outcomes.
Why it matters
Brain disorders can threaten health in later life. The authors identify blood metabolites as potential biomarkers to inform prevention.
Caveats
Participants with more pain sites also differed in smoking, weight and existing illnesses; these differences may partly account for the links despite statistical adjustments. The cohort excluded people who already had brain disorders.
Where the evidence stands
Inflammation
- 1,048 independent labs in 77 countries
- 205 findings against
- Funders: National Institutes of Health and others
- 382 of 4,615 findings with company ties
From the paper
- Participants
Leveraging data from 174,630 UK Biobank participants, we examined associations of 251 plasma metabolites with chronic pain across seven body sites and constructed a metabolic signature using elastic net regression.
- Follow-up
During a median follow-up of 15.6 years, an increasing number of chronic pain sites and a higher metabolic signature were associated with increased risks of depression, anxiety, and ischemic stroke (IS).
- Result
Specifically, a greater number of chronic pain sites was associated with the HR of 1.13 (95% CI: 1.11–1.14) for depression, 1.10 (95% CI: 1.09–1.12) for anxiety, and 1.04 (95% CI: 1.01–1.06) for IS (Table 2).
Results, 3.4 Associations of Chronic Pain With Brain Disorders
Quoted word for word from the full text on onlinelibrary.wiley.com.
The paper
Guangdong Provincial Clinical Research Center for Cancer Sun Yat-sen University Cancer Center Guangzhou China
CNS Neuroscience & Therapeutics, Nov 10, 2026, Open access, CC BY
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