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The val158met polymorphism of human catechol-O-methyltransferase (COMT) affects anterior cingulate cortex activation in response to painful laser stimulation

Arian Mobascher12*, Juergen Brinkmeyer23, Holger Thiele4, Mohammad R Toliat4, Michael Steffens5, Tracy Warbrick3, Francesco Musso2, Hans-Joerg Wittsack6, Andreas Saleh6, Alfons Schnitzler7 and Georg Winterer34

Author Affiliations

1 Department of Psychiatry, Johannes Gutenberg-University, Untere Zahlbacher Str. 8, 55131, Germany

2 Department of Psychiatry, Heinrich-Heine University, Bergische Landstr. 2, 40629 Duesseldorf, Germany

3 Institute of Neurosciences and Biophysics, Research Center Juelich, 52425 Juelich, Germany

4 Cologne Center for Genomics, Institute for Genetics, University of Cologne, Weyertal 115b, 50931 Köln, Germany

5 Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany

6 Institute of Radiology, Heinrich-Heine University, Moorenstr. 5, 40225 Duesseldorf, Germany

7 Insitute of Clinical Neurosciences and Medical Psychology, Heinrich-Heine University, Universitätsstr. 1, 40225 Duesseldorf, Germany

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Molecular Pain 2010, 6:32  doi:10.1186/1744-8069-6-32

Published: 31 May 2010



Pain is a complex experience with sensory, emotional and cognitive aspects. Genetic and environmental factors contribute to pain-related phenotypes such as chronic pain states. Genetic variations in the gene coding for catechol-O-methyltransferase (COMT) have been suggested to affect clinical and experimental pain-related phenotypes including regional μ-opioid system responses to painful stimulation as measured by ligand-PET (positron emission tomography). The functional val158met single nucleotide polymorphism has been most widely studied. However, apart from its impact on pain-induced opioid release the effect of this genetic variation on cerebral pain processing has not been studied with activation measures such as functional magnetic resonance imaging (fMRI), PET or electroencephalography. In the present fMRI study we therefore sought to investigate the impact of the COMT val158met polymorphism on the blood oxygen level-dependent (BOLD) response to painful laser stimulation.


57 subjects were studied. We found that subjects homozygous for the met158 allele exhibit a higher BOLD response in the anterior cingulate cortex (ACC), foremost in the mid-cingulate cortex, than carriers of the val158 allele.


This result is in line with previous studies that reported higher pain sensitivity in homozygous met carriers. It adds to the current literature in suggesting that this behavioral phenotype may be mediated by, or is at least associated with, increased ACC activity. More generally, apart from one report that focused on pain-induced opioid release, this is the first functional neuroimaging study showing an effect of the COMT val158met polymorphism on cerebral pain processing.