Neck Solutions

Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density

From: Journal of Neuroscience, November 17, 2004. 24(46):10410 –10415

The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. chronic back pain 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 chronic back pain 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 chronic back pain 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 chronic back pain. Our results imply that chronic back pain is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.

After correcting for age and gender, individual chronic back pain wholebrain gray matter volumes were lower than the mean of controls. Moreover, only 18% of whole-brain gray matter variance could be explained by pain duration. Therefore, a large portion of the whole-brain atrophy in chronic back pain cannot be accounted for by the measured pain characteristics, implying that there may be genetic and experiential predispositions contributing to the observed atrophy. In the dorsolateral prefrontal
cortex, a larger proportion of the variance could be explained by pain characteristics implying a tighter relationship between regional brain atrophy and perceived pain. Therefore, we suggest that the pattern of brain atrophy is directly related to the perceptual and behavioral properties of chronic back pain.

Given that, by definition, chronic pain is a state of continuous persistent perception with associated negative affect and stress, a parsimonious mechanistic explanation for the decreased gray matter is overuse atrophy caused by excitotoxicity and inflammatory agents potentiated by predisposing factors. We cannot rule out the contribution of possible lifestyle differences between the patients and control subjects to the observed differences in gray matter. However, we can assert the coexistence of theoretically independent effects (i.e., group differences in global and local brain gray matter volumes) determined by two independent methods (the association between global and regional densities with pain duration within the patient group and the association between regional densities and pain parameters within the patient group that also distinguishes between subtypes of chronic back pain) that provide compelling evidence for the importance of the observed morphometric changes in the pathophysiology of chronic back pain. We hypothesize that atrophy of the brain circuitry involved in pain perception may dictate the properties of the pain state, such that as atrophy of elements of the circuitry progresses, the pain condition becomes more irreversible and less responsive to therapy.