Structural brain alterations in chronic primary pain: a multimodal MRI study

Häuselmann, Salome; Wyss, Anna; Bischoff, Nina; Bruckmaier, Rupert; Gross, Josef; Berna, Chantal; grosse Holtforth, Martin; Aybek, Selma; Gninenko, Nicolas

doi:10.1016/j.nicl.2026.104023

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Journal article

Structural brain alterations in chronic primary pain: a multimodal MRI study

DOKPE

Häuselmann, Salome ORCID University of Bern
Wyss, Anna University of Bern
Bischoff, Nina University of Bern
Bruckmaier, Rupert ORCID University of Bern
Gross, Josef ORCID University of Bern
Berna, Chantal University of Lausanne
grosse Holtforth, Martin University of Bern
Aybek, Selma ORCID University of Fribourg
Gninenko, Nicolas ORCID University of Fribourg

2026

Published in:

NeuroImage: Clinical. - Elsevier BV. - 2026, vol. 51, p. 104023

English Chronic primary pain (CPP) occurs without an identifiable causal disease and is characterized by persistent pain,
emotional distress and functional impairment. Persistent pain may be accompanied by structural brain alterations
linked to chronification. We investigated cortical surface morphometry and structural connectivity in CPP
and explored associations with related biopsychosocial characteristics.
Thirty patients with CPP and 30 matched healthy controls (HCs) underwent psychometric assessment, pain
sensitivity testing, salivary sampling (cortisol, α-amylase), and MRI (T1-weighted, diffusion-weighted imaging
(DWI)). Surface-based morphometry features (SBM) were estimated from T1-weighted data across multiple brain
parcellations. DWI was used to reconstruct weighted structural connectomes via probabilistic tractography and
to compute node-level graph-theoretical metrics. Partial least squares correlation (PLSC) assessed multivariate
associations between imaging metrics and biopsychosocial characteristics.
Compared with HCs, CPP patients showed focal cortical alterations dominated by folding-related features
consistent across different brain parcellation schemes: increased gyrification in left prefrontal regions; reduced
sulcal depth in right lateral frontal and orbitofrontal and right medial temporo-occipital regions; and reduced
fractal dimension in posterior cingulate regions. Structural connectivity metrics showed only trend-level group
differences that did not survive correction for multiple comparisons.
PLSC revealed significant covariation between distributed SBM patterns and biopsychosocial characteristics,
including perceived stress, childhood trauma, and α-amylase concentration, mainly expressed in HCs, linking
stress-related features to profiles of gyrification, sulcal depth, and fractal dimension. These findings suggest that
cortical surface morphology may be structurally altered in patients with CPP and encourage further longitudinal
studies.

Faculty

Faculté des sciences et de médecine

Department

Section de médecine

Language