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Abstract

Pain states fluctuate over time and across situations. Similarly, there is variation in risk and protective factors and how they impact on these pain-related transitions. We are interested in whether such variations are more than random, and whether they can be accounted for by observed variables. The availability of large longitudinal datasets, such as UK Biobank ( https://www.ukbiobank.ac.uk/ ), offers a unique opportunity to study these variations at scale. However, such datasets bring a high risk of bias (eg, confounding) and danger of over-interpretation. It is therefore important to be transparent about our causal thinking. Directed acyclic graphs (DAGs) are graphical representations of the hypothesized causal relationships between variables. They are used to identify the smallest set of variables that need to be adjusted to remove confounding bias in estimating the causal effect of an exposure on an outcome. However, use of DAGs in pain research is not common, despite their potential to guide study design and data analysis. In this article, we present a workflow for building a DAG using domain knowledge from 3 different sources: researchers (theory-based), people with lived experience (person-based), and the literature (evidence-based). We created a DAG for the putative effect of executive function on the maintenance of chronic high-impact pain. The resulting DAG provides a valuable framework for guiding future research on the role of executive functioning in pain, and it underscores the broader potential of using DAGs to improve causal inference in pain research.

Original languageEnglish
Pages (from-to)414-427
Number of pages14
JournalPain
Volume167
Issue number2
Early online date28 Feb 2026
DOIs
Publication statusPublished - 28 Feb 2026

Data Availability Statement

No original datasets were generated or analysed during the course of this research.

Acknowledgements

The authors would like to extend our deepest gratitude to the individuals with lived experience who generously contributed their time, insights, and personal narrative to this work.

Funding

This work was supported by a joint and equal investment from UKRI (grant numbers MR/W004151/1, MR/W026872/1, and MR/W002388/1) and the charity vs Arthritis (grant number 22891) through the Advanced Pain Discovery Platform (APDP) initiative. For UKRI, the initiative is led by the Medical Research Council (MRC), with support from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Economic and Social Research Council (ESRC). G.C., A.D.P., C.E., E.F., and E.K. are part of the research scientific network grant PAIN, funded by the FWO (W001721N).

FundersFunder number
UK Research and Innovation Fund MR/W004151/1, MR/W026872/1, MR/W002388/1

    Keywords

    • Causality
    • Directed acyclic graphs
    • Executive functioning
    • Pain

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Anesthesiology and Pain Medicine

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