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Brain activations during pain: a neuroimaging meta-analysis of patients with pain and healthy controls

Jensen, Karin B.; Regenbogen, Christina; Ohse, Margarete C.; Frasnelli, Johannes; Freiherr, Jessica; Lundström, Johan N.

doi: 10.1097/j.pain.0000000000000517
Research Paper
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In response to recent publications from pain neuroimaging experiments, there has been a debate about the existence of a primary pain region in the brain. Yet, there are few meta-analyses providing assessments of the minimum cerebral denominators of pain. Here, we used a statistical meta-analysis method, called activation likelihood estimation, to define (1) core brain regions activated by pain per se, irrelevant of pain modality, paradigm, or participants and (2) activation likelihood estimation commonalities and differences between patients with chronic pain and healthy individuals. A subtraction analysis of 138 independent data sets revealed that the minimum denominator for activation across pain modalities and paradigms included the right insula, secondary sensory cortex, and right anterior cingulate cortex (ACC). Common activations for healthy subjects and patients with pain alike included the thalamus, ACC, insula, and cerebellum. A comparative analysis revealed that healthy individuals were more likely to activate the cingulum, thalamus, and insula. Our results point toward the central role of the insular cortex and ACC in pain processing, irrelevant of modality, body part, or clinical experience; thus, furthering the importance of ACC and insular activation as key regions for the human experience of pain.

Supplemental Digital Content is Available in the Text.The minimum denominators of pain processing in the human brain were explored by means of activation likelihood estimation, suggesting that the insula and ACC are essential for the experience of pain.

aDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

bClinic of Diagnostic and Interventional Neuroradiology, RWTH Aachen University, Aachen, Germany

cMonell Chemical Senses Center, University of Pennsylvania, Philadelphia, PA, USA

dCogNAC, Department of Anatomy, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada

eCÉAMS, Research Center, Sacré-Coeur Hospital, Montréal, QC, Canada

fDepartment of Psychology, University of Pennsylvania, Philadelphia, PA, USA

Corresponding author. Address: Department of Clinical Neuroscience, Karolinska Institutet, Nobels väg 9, D3, 17176 Stockholm, Sweden. Tel.: +46702130811; fax: +468311101. E-mail address: (K. B. Jensen).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received October 06, 2015

Received in revised form January 03, 2016

Accepted January 25, 2016

© 2016 International Association for the Study of Pain
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