Abnormal gray matter aging in chronic pain patients

Abstract Widespread brain gray matter (GM) atrophy is a normal part of the aging process. However, recent studies indicate that age-related GM changes are not uniform across the brain and may vary according to health status. Therefore the aims of this study were to determine whether chronic pain in temporomandibular disorder (TMD) is associated with abnormal GM aging in focal cortical regions associated with nociceptive processes, and the degree to which the cumulative effects of pain contributes to age effects. We found that patients have accelerated whole brain GM atrophy, compared to pain-free controls. We also identified three aberrant patterns of GM aging in five focal brain regions: 1) in the thalamus, GM volume correlated with age in the TMD patients but not in the control group; 2) in the anterior mid- and pregenual cingulate cortex (aMCC/pgACC), the TMD patients showed age-related cortical thinning, whereas the controls had age-related cortical thickening; and 3) in the dorsal striatum and the premotor cortex (PMC). Interestingly, the controls but not the patients showed age-related GM reductions. Finally, a result of particular note is that after accounting for the effects of TMD duration, age remained as a significant predictor of GM in the PMC and dorsal striatum. Thus, abnormal GM aging in TMD may be due to the progressive impact of TMD-related factors in pain-related regions, as well as inherent factors in motor regions, in patients with TMD. This study is the first to show that chronic pain is associated with abnormal GM aging in focal cortical regions associated with pain and motor processes.