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A PET activation study of brush-evoked allodynia in patientswith nerve injury pain

Witting, Nannaa,b,1,*; Kupers, Ron C.b,c,1; Svensson, Peterd,e; Jensen, Troels S.a

doi: 10.1016/j.pain.2005.10.034
Research papers

Acute experimental brush-evoked allodynia induces a cortical activation pattern that differs from that typically seen during experimental nociceptive pain. In this study, we used positron emission tomography to measure changes in regional cerebral blood flow (rCBF) in patients with clinical allodynia. Nine patients with peripheral nerve injury were scanned during rest, brush-evoked allodynia, and brushing of normal contralateral skin. PET data were analyzed for the whole group and for single subjects. Allodynic stimulation activated the contralateral orbitofrontal cortex (BA 11) in every patient. Whereas normal brushing activated most strongly the contralateral insular cortex, allodynic brushing produced an ipsilateral activation in this area. Another important difference between normal and allodynic brushing was the absence of a contralateral primary somatosensory cortex (SI) activation during allodynic brushing. No thalamic activation was observed during allodynic or control brushing. Although no anterior cingulate cortex (ACC) activation could be demonstrated in the group analysis, single subject analysis revealed that four patients activated this region during brush-evoked allodynia. A direct post hoc comparison of brush -and allodynia-induced rCBF changes showed that allodynia was associated with significantly stronger activations in orbitofrontal cortex and ipsilateral insula whereas non-painful brushing more strongly activated SI and BA 5/7. These findings indicate that activity in the cortical network involved in the sensory-discriminative processing of nociceptive pain is downregulated in neuropathic pain. Instead, there is an upregulation of activity in the orbitofrontal and insular cortices, which is probably due to the stronger emotional load of neuropathic pain and higher computational demands of processing a mixed sensation of brush and pain.

aDepartment of Neurology and Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark

bCFIN, Aarhus University and Aarhus University Hospital, Aarhus, Denmark

cPET unit and Department of Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark

dDepartment of Oral Maxillofacial Surgery, Aarhus University Hospital, Aarhus, Denmark

eDepartment of Clinical Oral Physiology, Royal Dental College, Aarhus, Denmark

*Corresponding author. Address: Danish Pain Research Center, Aarhus University Hospital, Building 1A, Noerrebrogade 44, DK-8000 Aarhus C, Denmark. Tel.: +45 89494137; fax: +45 89493269.

1Both these authors contributed equally to this work.


Submitted January 6, 2005; revised October 25, 2005; accepted October 31, 2005.

© 2006 Lippincott Williams & Wilkins, Inc.
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