Phenotype Matters: The Absence of a Positive Association Between Cortical Thinning and Chronic Low Back Pain When Controlling for Salient Clinical Variables

Abstract

Studies have associated chronic low back pain (cLBP) with grey matter thinning. But these studies have not controlled for important clinical variables (such as a comorbid affective disorder, pain medication, age, or pain phenotype), which may reduce or eliminate these associations. 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 (HCs).

An ROI-driven analysis (regions of interest) was conducted, using 18 clusters from a previous arterial spin labeling study demonstrating greater regional cerebral blood flow (rCBF) in these cLBP subjects than the HCs. Cortical thickness and VBM-based gray matter volume measurements were obtained from a structural MRI scan and group contrasts were calculated. MANOVA showed a trend toward cortical thickening in the right paracentral lobule in cLBP subjects (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 clusters were non-significant after including age as a covariate (p<0.891; p<0.279). A whole-brain cortical thickness and VBM analysis also did not identify significant clusters of thinning or thickening.

Exploratory analyses identified group differences for correlations between age and cortical thickness of the right rostral middle frontal gyrus (cLBP: R=-0.03, p=0.9; HCs: R=-0.81, p<0.001), i.e., HCs demonstrated age-related thinning while cLBP patients did not. Our pilot results suggest that controlling for affect, age, and concurrent medications may reduce or eliminate some of the previously reported structural brain alterations in cLBP.