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Cerebral Cortex Advance Access originally published online on November 13, 2006
Cerebral Cortex 2007 17(9):2050-2059; doi:10.1093/cercor/bhl113
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Discrete Changes in Cortical Activation during Experimentally Induced Referred Muscle Pain: A Single-Trial fMRI Study

Vaughan G. Macefield1, SC Gandevia1 and Luke A. Henderson2

1 Prince of Wales Medical Research Institute and the University of New South Wales, Sydney, NSW, Australia 2031, 2 Department of Anatomy and Histology, University of Sydney, Sydney, NSW, Australia 2006

Address correspondence to Luke A. Henderson, Department of Anatomy and Histology, University of Sydney, Sydney, NSW, Australia 2006. Email: lukeh{at}anatomy.usyd.edu.au.

Noxious stimulation of skeletal muscle evokes pain that is often referred into distal areas. Despite referred pain being of significant clinical importance, the brain regions responsible for the perception of referred pain remain unexplored. The aim of this investigation is to define these regions using functional magnetic resonance imaging. We induced muscle pain by hypertonic saline injections (0.5 ml) into the tibialis anterior (TA) or flexor carpi radialis (FCR) muscle. TA injections evoked pain that was referred to the ankle/foot in 10/17 subjects, whereas FCR injections evoked pain that was projected into the wrist/hand in 6/12 subjects. Regional brain responses were statistically tested by convolving the temporal profile of the subjective pain intensity rating with the hemodynamic response function. For all subjects, signal increased in the region of primary somatosensory cortex (SI), which represents the leg or arm, that is, the area corresponding to the injection site. However, for those subjects who reported referred pain, signal intensity increases also occurred in the SI region representing the foot or hand. Interestingly, differential signal changes also occurred in anterior cingulate, cerebellar, and insular cortices. This is the first study to provide evidence of cortical differentiation in the processing of primary and referred pain.

Key Words: anterior cingulate cortex • cerebellum • insula • somatosensory cortex • somatotopy


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