Chronic back pain is associated with decreased prefrontal and thalamic gray matter density

Abstract

The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain (CBP) patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. CBP patients were divided into neuropathic, exhibiting pain because of sciatic nerve damage, and non-neuropathic groups. Pain-related characteristics were correlated to morphometric measures. Neocortical gray matter volume was compared after skull normalization. Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10-20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm3 loss of gray matter for every year of chronic pain. Regional gray matter density in 17 CBP patients was compared with matched controls using voxel-based morphometry and nonparametric statistics. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic CBP. Our results imply that CBP is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.

Figure 3.

DLPFC gray matter density as a function of subtypes of CBP. A, DLPFC gray matter density is highest in controls and lowest in neuropathic patients. Gray matter density is in arbitrary units derived from regional eigenvariates. B, Somatotopy of pain is shown on the figurines to the right, for subtypes of CBP. Color code is the number of subjects localizing their pain to indicated body site. Only the 17 CBP patients used in VBM are shown. The remaining CBP patients had a similar somatotopy for CBP.

Figure 1.

Decreased whole-brain cortical gray matter volume in CBP subjects. Skull-normalized neocortical gray matter volumes are shown for CBP subjects and matched control subjects. A, Gray matter volumes as a function of age. The difference in intercepts corresponds to an average decrease of 30 cm³ in gray matter volume in CBP compared with the normal subjects. B, Gray matter volumes as a function of pain duration, after correcting for age and gender. Individual control subjects are shown at pain duration = 0. nuCBP and non-nuCBP CBP patient data are presented separately. The horizontal line is the mean volume for controls. Individual whole-brain gray matter volumes in CBP subjects are all below the mean volume for controls. Group-averaged gray matter volumes (mean ± SEM) are shown in the right bar graph, before (top) and after (bottom) correcting for age and gender. Lines are best linear fits for each group.

Figure 2.

Regional gray matter density decreases in CBP subjects. A nonparametric comparison of voxel-based morphometry between CBP and control subjects is shown. A, Gray matter density is bilaterally reduced in the DLPFC. The result is from a VBM permutation-based pseudo-t test and voxel-level contrasts when all brain gray matter voxels were compared between controls and CBP subjects. Pseudocolor highly positive values indicate regions where gray matter density was reduced in CBP subjects (controls - CBP). B, A nonparametric comparison spatially limited to the thalami revealed a significant decrease in gray matter density in the right anterior thalamus. A slice at the peak of decreased thalamic gray matter is shown. Pseudo-t values are color coded; range is 3-6.