Phenotype matters: the importance of age, affect, medication, and pain characterization in the brain morphometry of chronic low back pain

Chronic low back pain (cLBP) is believed to be associated with alterations in brain morphometry. Studies have reported significant grey matter thinning, but they have not carefully controlled for important variables, such as affective disorder, pain medication, age, and pain phenotype. We propose that controlling for these factors may reduce the magnitude of the reported brain alterations in cLBP. We conducted cortical thickness and voxel-based morphometry (VBM) analyses in 14 cLBP patients with a discogenic component to their pain, not taking opioids or benzodiazepines, and not depressed or anxious. They were age and gender matched to 14 healthy controls (HC). An ROI-driven analysis was conducted, using 18 clusters from a previous arterial spin labeling (ASL) study identifying brain regions more active in cLBP subjects than HC during exacerbated back pain. Cortical thickness measurements were obtained from each subject’s structural MRI scan after being processed within the automated FreeSurfer cortical reconstruction pipeline. VBM analysis was conducted within SPM8 contrasting grey matter volume between groups. MANOVA showed cLBP subject mild cortical thickening in the right paracentral lobule (F(1,17)=3.667, p<0.067) and significant thickening in the right rostral middle frontal gyrus (F(1,17)=6.880, p<0.014). These areas did not hold significance after including age as a covariate (p<0.891; p<0.279 respectively). A follow-up whole-brain analysis also did not identify significant clusters. VBM did not identify any significant clusters after controlling for multiple comparisons (uncorrected clusters p<0.001, false discovery rate correction p<0.05). Exploratory analyses identified a dichotomous trend in the correlation of age and cortical thickness of the right rostral middle frontal gyrus between cLBP subjects (R=-0.027, p< 0.928) and HC (R=-0.805, p< 0.001). Our pilot results suggest that affect, age, and concurrent medications may account for part of the previously reported brain alterations in cLBP. Follow-up studies should include a larger sample and explore possible cortical thickening.