title: Phenotype matters: the absence of a positive association between cortical thinning and chronic low back pain when controlling for salient clinical variables.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 pain-free controls (PFCs). 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 PFCs. Cortical thickness and VBM-based gray matter volume measurements were obtained from a structural MRI scan and group contrasts were calculated.
  
  
  RESULTS
  Multivariate analysis of variance showed a trend toward cortical thickening in the right paracentral lobule in cLBP subjects (F1,17=3.667, P<0.067), and significant thickening in the right rostral middle frontal gyrus (F1,17=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; PFCs: R=-0.81, P<0.001), that is, PFCs demonstrated age-related thinning while cLBP patients did not.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of *Anesthesiology §Psychiatry, Brigham and Women's Hospital Departments of †Radiology ‡Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA Departments of ∥Anesthesiology ¶Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dolman
authors.forename: Marco L
authors.initials: ML
authors.lastname: Loggia
authors.forename: Robert R
authors.initials: RR
authors.lastname: Edwards
authors.forename: Randy L
authors.initials: RL
authors.lastname: Gollub
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Wasan
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology*; D002908:Chronic Disease; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017116:Low Back Pain / Q000150:complications / Q000473:pathology* / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000209:etiology; D010147:Pain Measurement; D010641:Phenotype; D011569:Psychiatric Status Rating Scales