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Brain Advance Access originally published online on September 2, 2006
Brain 2006 129(11):2957-2965; doi:10.1093/brain/awl228
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© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Pain sensitivity and fMRI pain-related brain activity in Alzheimer's disease

Leonie J. Cole1,2,5, Michael J. Farrell1,2,5, Eugene P. Duff1,3, J. Bruce Barber5, Gary F. Egan1,2 and Stephen J. Gibson4,5

1 Howard Florey Institute, University of Melbourne Parkville, Victoria, Australia 2 Centre for Neuroscience, University of Melbourne Parkville, Victoria, Australia 3 Department of Mathematics and Statistics, University of Melbourne Parkville, Victoria, Australia 4 Department of Medicine, University of Melbourne, University of Melbourne Parkville, Victoria, Australia 5 National Ageing Research Institute Parkville, Victoria, Australia

Correspondence to: Leonie J. Cole, Howard Florey Institute, University of Melbourne, Parkville, Victoria 3010, Australia E-mail: l.cole{at}hfi.unimelb.edu.au

People with Alzheimer's disease are administered fewer analgesics and report less clinical pain than cognitively intact peers with similar painful diseases or injuries, prompting speculation about the likely impact of neurodegeneration on central pain processing. The present study measured pain ratings and functional MRI (fMRI) brain responses following mechanical pressure simulation in 14 patients with Alzheimer's disease and 15 age-matched controls. Contrary to the prevailing hypothesis that this disease is likely to differentially reduce emotional responses to pain, we show that activity in both medial and lateral pain pathways is preserved. Moderate pain was evoked with similar stimuli in both groups, and was associated with a common network of pain-related activity incorporating cingulate, insula and somatosensory cortices. Between-group analyses showed no evidence of diminished pain-related activity in Alzheimer's disease patients compared with controls. In fact, compared with controls, patients showed greater amplitude and duration of pain-related activity in sensory, affective and cognitive processing regions consistent with sustained attention to the noxious stimulus. The results of this study show that pain perception and processing are not diminished in Alzheimer's disease, thereby raising concerns about the current inadequate treatment of pain in this highly dependent and vulnerable patient group.

Key Words: Alzheimer's disease; pain; fMRI; aged

Abbreviations: aMCC, anterior midcingulate cortex; BA, Brodmann area; BOLD, blood oxygen level-dependent; DLPFC, dorsolateral prefrontal cortex; fMRI, functional magnetic resonance imaging; IC, insula cortex; JNP, just noticeable pain; M1, primary motor cortex; MMSE, Mini-Mental State Examination; MP, moderate pain; ROI, region of interest; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; WP, weak pain

Received March 24, 2006. Revised July 17, 2006. Accepted July 25, 2006.


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