Structural brain alterations in chronic primary pain: a multimodal MRI study.
Cortical surface morphology may be altered in chronic primary pain, but structural connectivity findings require further validation.
Where it sits
this study against the rest of the tesofensine corpusSummary and findings
This study assessed cortical surface morphometry and structural connectivity in 30 patients with chronic primary pain (CPP) compared to 30 healthy controls. MRI data revealed cortical alterations in CPP patients, including increased gyrification in left prefrontal regions and reduced sulcal depth in various brain areas. Structural connectivity differences were observed but did not reach statistical significance after correction.
Abstract
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.
Background
Chronic primary pain (CPP) is a condition characterized by persistent pain without an identifiable cause, often accompanied by emotional distress and functional impairment. Previous research suggests that structural brain alterations may be associated with the chronification of pain. This study aims to explore these potential alterations using advanced MRI techniques to better understand the underlying neurobiological mechanisms of CPP.
Methods
The study involved 30 patients with CPP and 30 matched healthy controls who underwent psychometric assessments, pain sensitivity testing, salivary sampling, and MRI scans. T1-weighted and diffusion-weighted imaging (DWI) were used to assess cortical surface morphometry and structural connectivity. Surface-based morphometry features were estimated across multiple brain parcellations, and probabilistic tractography was used to reconstruct weighted structural connectomes. Partial least squares correlation (PLSC) was employed to assess associations between imaging metrics and biopsychosocial characteristics.
Results
The primary findings indicated focal cortical alterations in CPP patients, including increased gyrification in the left prefrontal regions and reduced sulcal depth in the right lateral frontal, orbitofrontal, and right medial temporo-occipital regions. Additionally, a reduced fractal dimension was observed in the posterior cingulate regions. Structural connectivity metrics showed trend-level differences between groups, but these did not survive correction for multiple comparisons. PLSC analysis revealed significant covariation between distributed SBM patterns and biopsychosocial characteristics, particularly in healthy controls.
Interpretation
The study identifies specific cortical surface morphology changes in CPP patients, suggesting potential structural brain alterations linked to chronic pain. However, the lack of statistically significant findings in structural connectivity metrics after correction limits the conclusions. These results align with previous literature indicating brain structure changes in chronic pain conditions, but further research is needed to establish clinical significance and causality. The study's cross-sectional design and small sample size are notable limitations.
Key findings
- 30 patients with CPP and 30 matched healthy controls were studied.
- Increased gyrification in left prefrontal regions in CPP patients.
- Reduced sulcal depth in right lateral frontal, orbitofrontal, and right medial temporo-occipital regions in CPP patients.
- Reduced fractal dimension in posterior cingulate regions in CPP patients.
- Structural connectivity metrics showed trend-level differences not surviving correction.
Limitations
- Small sample size of n=30 per group.
- Structural connectivity findings did not survive correction for multiple comparisons.
- Cross-sectional design limits causal inference.
- Single-site study may limit generalizability.