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Building causal models in pain research: the case of executive functioning and transitions in pain states

Building causal models in pain research: the case of executive functioning and transitions in pain states
Building causal models in pain research: the case of executive functioning and transitions in pain states
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.
Causality, Directed acyclic graphs, Executive functioning, Pain
0304-3959
414-427
De Paepe, Annick L.
35d8a37a-7888-4045-a672-65d693c5e561
Gibby, Anna
c1192e50-f189-4fc7-a82f-1fe89795e6b0
Oporto-Lisboa, Laura
32e58fb6-4bc9-4e3f-a66d-959f426ad5a2
Ehrhardt, Beate
e668bb6c-99ca-43cf-857f-f5298a6cc930
Nunes, Matthew
925d2e9f-8185-4479-aaf4-55fa45b83e1f
Fisher, Emma
ece7e418-2af2-441a-a5c4-528abd7c434d
Keogh, Edmund
c59c78dd-bfa2-4aa5-8fd8-d83550c5f378
Eccleston, Christopher
5af6a4a9-c83b-43ba-800d-e30e9be2d1a2
Woolley, Charlotte
a7489a54-bb5f-4c69-b0b2-50e0c1a3d01b
McBeth, John
98012716-66ba-480b-9e43-ac53b51dce61
Crombez, Geert
704e24df-10a6-4808-81ae-8ad87d8b8569
De Paepe, Annick L.
35d8a37a-7888-4045-a672-65d693c5e561
Gibby, Anna
c1192e50-f189-4fc7-a82f-1fe89795e6b0
Oporto-Lisboa, Laura
32e58fb6-4bc9-4e3f-a66d-959f426ad5a2
Ehrhardt, Beate
e668bb6c-99ca-43cf-857f-f5298a6cc930
Nunes, Matthew
925d2e9f-8185-4479-aaf4-55fa45b83e1f
Fisher, Emma
ece7e418-2af2-441a-a5c4-528abd7c434d
Keogh, Edmund
c59c78dd-bfa2-4aa5-8fd8-d83550c5f378
Eccleston, Christopher
5af6a4a9-c83b-43ba-800d-e30e9be2d1a2
Woolley, Charlotte
a7489a54-bb5f-4c69-b0b2-50e0c1a3d01b
McBeth, John
98012716-66ba-480b-9e43-ac53b51dce61
Crombez, Geert
704e24df-10a6-4808-81ae-8ad87d8b8569

De Paepe, Annick L., Gibby, Anna, Oporto-Lisboa, Laura, Ehrhardt, Beate, Nunes, Matthew, Fisher, Emma, Keogh, Edmund, Eccleston, Christopher, Woolley, Charlotte, McBeth, John and Crombez, Geert (2026) Building causal models in pain research: the case of executive functioning and transitions in pain states. Pain, 167 (2), 414-427. (doi:10.1097/j.pain.0000000000003833).

Record type: Article

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.

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Accepted/In Press date: 6 August 2025
e-pub ahead of print date: 22 October 2025
Published date: 1 February 2026
Keywords: Causality, Directed acyclic graphs, Executive functioning, Pain

Identifiers

Local EPrints ID: 510243
URI: http://eprints.soton.ac.uk/id/eprint/510243
ISSN: 0304-3959
PURE UUID: fcac55c7-05ec-4bb8-9977-5742813c7faf
ORCID for John McBeth: ORCID iD orcid.org/0000-0001-7047-2183

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Date deposited: 24 Mar 2026 17:36
Last modified: 25 Mar 2026 03:14

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Contributors

Author: Annick L. De Paepe
Author: Anna Gibby
Author: Laura Oporto-Lisboa
Author: Beate Ehrhardt
Author: Matthew Nunes
Author: Emma Fisher
Author: Edmund Keogh
Author: Christopher Eccleston
Author: Charlotte Woolley
Author: John McBeth ORCID iD
Author: Geert Crombez

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