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

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.