Voxel based morphometry analysis of patients with chronic neuropathic pain

Complex regional pain syndrome (CRPS) is a debilitating chronic neuropathic pain condition. Central mechanisms have been proposed to play a role in the generation and maintenance of many chronic pain conditions. In this study we investigated regional gray matter volume (GMV) differences between CRPS patients and controls by performing voxel-based morphometry (VBM) analyses on high-resolution T1 magnetic resonance images. Eighteen right-handed patients with right upper extremity CRPS (mean age 41.7+11.3 (SD)) meeting IASP criteria for CRPS were matched with 25 right-handed controls (age 35.0+14.0). Statistical Parametrical Mapping 5 (SPM5) software and tools provided by Dr. Christian Gaser were used to process the data. Gray matter (GM) images were then submitted to an analysis of covariance (ANCOVA) regressing out age and total GMV (p=0.01 corrected). We found that CRPS patients, compared to controls, had significantly reduced GM in the cingulate to precuneus and increased GM in the right occipital cerebellar region. At a more lenient threshold, we found increased GM in the left lateral prefrontal region and the midbrain including periaqueductal gray. A second analysis (CRPS: n15, age 43.7 ± 9.1 RH females with right upper-extremity CRPS; Controls: n15, age 41.6 ±12.8, RH females) showed similar trends. The increase in cerebellar volume may be due to repeated painful stimuli being processed through the cerebello-thalamo-cortical pathways. Increases in periaqueductal gray may represent continued increased inhibitory activity in patients with chronic pain. The posterior cingulate and the precuneus are thought to be involved in the experience of pain -- the posterior cingulate through the encoding of pain intensity, and the precuneas through emotional learning and integrative tasks. The areas of decreased GM are shown in functional studies to be hyperactive in pain patients adds further support to the theory that CRPS induces structural abnormalities in the human brain.