Abnormal gray matter aging in chronic pain patients

Massieh Moayedi, Irit Weissman-Fogel, Tim V. Salomons, Adrian P. Crawley, Michael B. Goldberg, Bruce V. Freeman, Howard C. Tenenbaum, Karen D. Davis

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)82-93
Number of pages12
JournalBrain Research
StatePublished - 25 May 2012
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a Canadian Institute of Health Research (CIHR) grant and funds from the Canada Research Chair program [MOP 53304] (to KDD); CIHR studentship (to MM); Ontario Graduate Scholarship (to MM); CIHR Strategic Training programs: Pain: Molecules to Community (to MM and IWF), and Cell Signals in Mucosal Inflammation and Pain [STP-53877] (to MM); University of Toronto Centre for the Study of Pain Clinician/Scientist Research fellowship (to IWF and TVS).


  • Aging
  • Chronic pain
  • Cortical thickness analysis
  • MRI
  • Temporomandibular disorder
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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