Distinct Grey Matter Alterations in Untreated Mild to Moderate Chronic Low Back Pain: A Longitudinal Magnetic Resonance Imaging Study

BACKGROUND: Chronic low back pain (CLBP) remains the leading cause of disability worldwide, yet lumbar structural abnormalities seldom account for reported symptoms. Prior neuroimaging studies often report reduced cerebral grey matter density (GMD) in CLBP but typically include patients with moderate-to-severe pain who are taking centrally acting medications, both of which can independently influence brain structure. METHODS AND RESULTS: This longitudinal observational cohort study assessed GMD in mostly mild-to-moderate CLBP individuals not using centrally acting medications. High-resolution T1-weighted MRI scans were acquired over three timepoints (baseline, 2 months, and 4 months) from 27 CLBP participants and 25 matched healthy controls. Voxel-based morphometry revealed significantly increased GMD in CLBP participants in the right middle frontal and temporal gyri, and left orbitofrontal cortex. Additionally, GMD in regions including the right inferior parietal lobule (rIPL) showed an inverse correlation with global pain severity across all timepoints (r up to -0.72, p < 0.0001). Participants with longer pain duration (≥ 5 years) showed lower GMD in the rIPL and reported greater symptom severity, independent of age. CONCLUSIONS: Brain structural alterations may be present even in mild, unmedicated CLBP and may vary depending on pain duration and intensity. Structural variation in the rIPL was consistently associated with pain severity, suggesting that this region may contribute to inter-individual differences in symptom burden. Given the correlational nature of these findings, future well-controlled longitudinal studies spanning the full spectrum of chronic low back pain severity and treatment exposure are warranted to clarify the temporal dynamics and clinical relevance of these structural differences. SIGNIFICANCE STATEMENT: This study demonstrates that individuals with mild, unmedicated chronic low back pain show increased grey matter density in frontal and temporal regions and a robust inverse association between pain severity and parietal grey matter. By identifying the right inferior parietal lobule as a neural marker linked to symptom intensity, these findings refine our understanding of pain-related brain plasticity, highlight structural correlates present even in less severe clinical populations, and suggest novel targets for early intervention strategies in chronic pain.